This study determined the biochemical composition of the adductor muscle and mantle of two species of the giant clams Tridacna crocea and Tridacna squamosa harvested from the lagoon of South China Sea. Moisture, crude protein, crude lipid, and ash contents of the giant clams (% wet weight) ranged 77.01%–81.47%, 10.90%–15.59%, 0.39%–1.02%, and 2.25%–3.23%, respectively, with some significant differences between species and tissues (P < 0.05). The total amino acid and essential amino acid contents of the adductor muscle were 62.20–61.07 g/100 g and 24.89–24.80 g/100 g, respectively, significantly higher than those in the mantle (52.80–55.98 g/100 g and 17.85–19.73 g/100 g, respectively) (P < 0.05). Total saturated fatty acids (SFA) were found to be higher than total monounsaturated fatty acids (MUFA) and polyunsaturated fatty acids (PUFA), accounting for 41.53%–55.40% for SFA, 25.83%–27.31% for MUFA, and 18.63%–31.25% for PUFA. There was no difference between the MUFA profiles of T. crocea and T. squamosa, whereas the PUFA profiles in T. squamosa were significantly higher than those in T. crocea (P < 0.05). The ratios of total n-3 PUFA to n-6 PUFA were the highest in the mantle of T. squamosa (6.60), followed by the mantle of T. crocea (2.54), and finally, the adductor muscle of T. crocea (1.82) and T. squamosa (1.09). Therefore, these two giant clam species, T. crocea and T. squamosa, are excellent sources of several nutrients that could be beneficial for the health of consumers.