A high-speed multi-channel data transmission method is disclosed. The method includes that: a data sender replaces data at intervals of N periods with frame headers in data channels, sequentially stores the data replaced with the frame headers in the data channels in a Deskew channel, and sends the data in the data channels and data in the Deskew channel to a data receiver; the data receiver determines frame header locations of the data channels and the Deskew channel, calculates offsets of the data channels according to the frame header locations, and performs period compensation for the data channels according to the calculated offsets to keep the frame header of each data channel and the frame header of the Deskew channel in a relative relationship the same as that at the data sender; and the frame headers on the data channels and the corresponding data on the Deskew channel are replaced to finish data restoration. A high-speed multi-channel data transmission system and related devices are further disclosed. According to the embodiments of the disclosure, 400 Gb/s multi-channel data alignment and restoration can be realized, and speed of data alignment and restoration is increased.