diff --git a/cpp/src/arrow/c/helpers.h b/cpp/src/arrow/c/helpers.h
index 6e4df17f43eb..66ba485bb109 100644
--- a/cpp/src/arrow/c/helpers.h
+++ b/cpp/src/arrow/c/helpers.h
@@ -57,8 +57,17 @@ inline void ArrowSchemaMove(struct ArrowSchema* src, struct ArrowSchema* dest) {
   ArrowSchemaMarkReleased(src);
 }
 
+/// The release callback can be implemented outside the code built with Clang CFI, for
+/// example in another language such as Rust. It then has no CFI type, so this call
+/// cannot be checked.
+#if defined(__clang__)
+#define ARROW_C_RELEASE_NO_CFI __attribute__((no_sanitize("cfi-icall")))
+#else
+#define ARROW_C_RELEASE_NO_CFI
+#endif
+
 /// Release the C schema, if necessary, by calling its release callback
-inline void ArrowSchemaRelease(struct ArrowSchema* schema) {
+ARROW_C_RELEASE_NO_CFI inline void ArrowSchemaRelease(struct ArrowSchema* schema) {
   if (!ArrowSchemaIsReleased(schema)) {
     schema->release(schema);
     ARROW_C_ASSERT(ArrowSchemaIsReleased(schema),
@@ -102,7 +111,7 @@ inline void ArrowDeviceArrayMove(struct ArrowDeviceArray* src,
 }
 
 /// Release the C array, if necessary, by calling its release callback
-inline void ArrowArrayRelease(struct ArrowArray* array) {
+ARROW_C_RELEASE_NO_CFI inline void ArrowArrayRelease(struct ArrowArray* array) {
   if (!ArrowArrayIsReleased(array)) {
     array->release(array);
     ARROW_C_ASSERT(ArrowArrayIsReleased(array),
diff --git a/cpp/src/arrow/flight/transport/grpc/customize_grpc.h b/cpp/src/arrow/flight/transport/grpc/customize_grpc.h
index 7836f7c161d6..99e8e4e9927b 100644
--- a/cpp/src/arrow/flight/transport/grpc/customize_grpc.h
+++ b/cpp/src/arrow/flight/transport/grpc/customize_grpc.h
@@ -86,6 +86,13 @@ ::grpc::Status FlightDataSerialize(const arrow::flight::FlightPayload& msg,
 // protobuf without copying
 ARROW_FLIGHT_EXPORT ::grpc::Status FlightDataDeserialize(
     ::grpc::ByteBuffer* buffer, arrow::flight::internal::FlightData* out);
+
+// The Arrow structs carried by the `pb::FlightData` messages that WritePayload()
+// and ReadPayload() give to gRPC (see serialization_internal.cc).
+ARROW_FLIGHT_EXPORT const arrow::flight::FlightPayload& FlightPayloadOfMessage(
+    const void* message);
+ARROW_FLIGHT_EXPORT arrow::flight::internal::FlightData* FlightDataOfMessage(
+    void* message);
 }  // namespace grpc
 }  // namespace transport
 }  // namespace flight
@@ -102,16 +109,16 @@ class SerializationTraits<arrow::flight::protocol::FlightData> {
 #endif
 
  public:
-  // In the functions below, we cast back the Message argument to its real
-  // type (see ReadPayload() and WritePayload() for the initial cast).
+  // The message carries the Arrow struct to serialize or to deserialize into
+  // (see ReadPayload() and WritePayload()).
   static Status Serialize(const MessageType& msg, ByteBuffer* bb, bool* own_buffer) {
     return arrow::flight::transport::grpc::FlightDataSerialize(
-        *reinterpret_cast<const arrow::flight::FlightPayload*>(&msg), bb, own_buffer);
+        arrow::flight::transport::grpc::FlightPayloadOfMessage(&msg), bb, own_buffer);
   }
 
   static Status Deserialize(ByteBuffer* buffer, MessageType* msg) {
     return arrow::flight::transport::grpc::FlightDataDeserialize(
-        buffer, reinterpret_cast<arrow::flight::internal::FlightData*>(msg));
+        buffer, arrow::flight::transport::grpc::FlightDataOfMessage(msg));
   }
 };
 
diff --git a/cpp/src/arrow/flight/transport/grpc/serialization_internal.cc b/cpp/src/arrow/flight/transport/grpc/serialization_internal.cc
index ee13a8e2022f..ec5c9462263c 100644
--- a/cpp/src/arrow/flight/transport/grpc/serialization_internal.cc
+++ b/cpp/src/arrow/flight/transport/grpc/serialization_internal.cc
@@ -17,6 +17,7 @@
 
 #include "arrow/flight/transport/grpc/serialization_internal.h"
 
+#include <cstddef>
 #include <cstdint>
 #include <memory>
 #include <string>
@@ -203,72 +204,103 @@ ::grpc::Status FlightDataDeserialize(ByteBuffer* buffer,
 #  pragma GCC diagnostic ignored "-Wstrict-aliasing"
 #endif
 
-// Pointer bitcast explanation: grpc::*Writer<T>::Write() and grpc::*Reader<T>::Read()
-// both take a T* argument (here pb::FlightData*).  But they don't do anything
-// with that argument except pass it to SerializationTraits<T>::Serialize() and
-// SerializationTraits<T>::Deserialize().
-//
-// Since we control SerializationTraits<pb::FlightData>, we can interpret the
-// pointer argument whichever way we want, including cast it back to the original type.
-// (see customize_grpc.h).
+// grpc::*Writer<T>::Write() and grpc::*Reader<T>::Read() take a T (here
+// pb::FlightData) and only pass it to SerializationTraits<T>::Serialize() and
+// SerializationTraits<T>::Deserialize(), which we control (see customize_grpc.h).
+// So instead of building the protobuf message, we give gRPC an empty, real
+// pb::FlightData that carries the Arrow struct, and the traits read the struct
+// from it. The message must be a real pb::FlightData: an Arrow struct cast to
+// pb::FlightData is not one, which is undefined behavior and which Clang CFI
+// (`-fsanitize=cfi-unrelated-cast`) rejects.
+
+namespace {
+
+struct FlightPayloadMessage {
+  pb::FlightData message;
+  const FlightPayload* payload;
+};
+
+struct FlightDataMessage {
+  pb::FlightData message;
+  flight::internal::FlightData* data;
+};
+
+}  // namespace
+
+// `message` points to the `message` member of one of the structs above.
+const FlightPayload& FlightPayloadOfMessage(const void* message) {
+  return *reinterpret_cast<const FlightPayloadMessage*>(
+              static_cast<const char*>(message) - offsetof(FlightPayloadMessage, message))
+              ->payload;
+}
+
+flight::internal::FlightData* FlightDataOfMessage(void* message) {
+  return reinterpret_cast<FlightDataMessage*>(static_cast<char*>(message) -
+                                              offsetof(FlightDataMessage, message))
+      ->data;
+}
 
 arrow::Result<bool> WritePayload(
     const FlightPayload& payload,
     ::grpc::ClientReaderWriter<pb::FlightData, pb::PutResult>* writer) {
   RETURN_NOT_OK(payload.Validate());
-  // Pretend to be pb::FlightData and intercept in SerializationTraits
-  return writer->Write(*reinterpret_cast<const pb::FlightData*>(&payload),
-                       ::grpc::WriteOptions());
+  FlightPayloadMessage message;
+  message.payload = &payload;
+  return writer->Write(message.message, ::grpc::WriteOptions());
 }
 
 arrow::Result<bool> WritePayload(
     const FlightPayload& payload,
     ::grpc::ClientReaderWriter<pb::FlightData, pb::FlightData>* writer) {
   RETURN_NOT_OK(payload.Validate());
-  // Pretend to be pb::FlightData and intercept in SerializationTraits
-  return writer->Write(*reinterpret_cast<const pb::FlightData*>(&payload),
-                       ::grpc::WriteOptions());
+  FlightPayloadMessage message;
+  message.payload = &payload;
+  return writer->Write(message.message, ::grpc::WriteOptions());
 }
 
 arrow::Result<bool> WritePayload(
     const FlightPayload& payload,
     ::grpc::ServerReaderWriter<pb::FlightData, pb::FlightData>* writer) {
   RETURN_NOT_OK(payload.Validate());
-  // Pretend to be pb::FlightData and intercept in SerializationTraits
-  return writer->Write(*reinterpret_cast<const pb::FlightData*>(&payload),
-                       ::grpc::WriteOptions());
+  FlightPayloadMessage message;
+  message.payload = &payload;
+  return writer->Write(message.message, ::grpc::WriteOptions());
 }
 
 arrow::Result<bool> WritePayload(const FlightPayload& payload,
                                  ::grpc::ServerWriter<pb::FlightData>* writer) {
   RETURN_NOT_OK(payload.Validate());
-  // Pretend to be pb::FlightData and intercept in SerializationTraits
-  return writer->Write(*reinterpret_cast<const pb::FlightData*>(&payload),
-                       ::grpc::WriteOptions());
+  FlightPayloadMessage message;
+  message.payload = &payload;
+  return writer->Write(message.message, ::grpc::WriteOptions());
 }
 
 bool ReadPayload(::grpc::ClientReader<pb::FlightData>* reader,
                  flight::internal::FlightData* data) {
-  // Pretend to be pb::FlightData and intercept in SerializationTraits
-  return reader->Read(reinterpret_cast<pb::FlightData*>(data));
+  FlightDataMessage message;
+  message.data = data;
+  return reader->Read(&message.message);
 }
 
 bool ReadPayload(::grpc::ClientReaderWriter<pb::FlightData, pb::FlightData>* reader,
                  flight::internal::FlightData* data) {
-  // Pretend to be pb::FlightData and intercept in SerializationTraits
-  return reader->Read(reinterpret_cast<pb::FlightData*>(data));
+  FlightDataMessage message;
+  message.data = data;
+  return reader->Read(&message.message);
 }
 
 bool ReadPayload(::grpc::ServerReaderWriter<pb::PutResult, pb::FlightData>* reader,
                  flight::internal::FlightData* data) {
-  // Pretend to be pb::FlightData and intercept in SerializationTraits
-  return reader->Read(reinterpret_cast<pb::FlightData*>(data));
+  FlightDataMessage message;
+  message.data = data;
+  return reader->Read(&message.message);
 }
 
 bool ReadPayload(::grpc::ServerReaderWriter<pb::FlightData, pb::FlightData>* reader,
                  flight::internal::FlightData* data) {
-  // Pretend to be pb::FlightData and intercept in SerializationTraits
-  return reader->Read(reinterpret_cast<pb::FlightData*>(data));
+  FlightDataMessage message;
+  message.data = data;
+  return reader->Read(&message.message);
 }
 
 bool ReadPayload(::grpc::ClientReaderWriter<pb::FlightData, pb::PutResult>* reader,