Razor clams, which are rich in diverse lipids, are notable for their unique health benefits and functional properties. This study comprehensively characterized and compared the composition and bioactivities of razor clam lipids after freeze drying (FD) and hot air drying (HD) using UPLC-MS/MS-based lipidomics and zebrafish models. Lipidomics analysis identified 1056 lipids classified into five lipid classes, among which glycerophospholipid (GP) was the most abundant, accounting for 57.39% of the total lipids. The total lipids were also grouped into 24 lipid subclasses, including dominated triglycerides, phosphatidylethanolamines, and phosphatidylcholines. Differential lipid species were identified between the FD, HD, and fresh (FS) sample groups, with 174, 141, and 154 species differing between FD vs. FS, HD vs. FS, and FD vs. HD, respectively. The antithrombotic, anti-inflammatory, and antioxidant activities of lipids extracted from FD, HD, and FS razor clams were evaluated using the zebrafish model. Lipids from FD and FS razor clams exhibited all bioactivities at some concentrations, while HD lipids showed antithrombotic and anti-inflammatory activities but lacked antioxidant activity. In summary, the lipid composition and bioactivities of fresh razor clams were altered following FD and HD processes, with significant differences observed between the two methods. These findings underscore the nutritional value of fresh razor clams after processing and provide insights for developing razor clam products.