Swietenia macrophylla has been used in treatments for diabetes, asthma, premenstrual syndrome and migraine traditionally. The seeds of S. macrophylla have been proven to possess antioxidant, antimicrobial, antifungal and hyperglycemic activity. Supercritical carbon dioxide (SC-CO2) extraction is a recent extraction process technology that has been developed to provide better extraction yield, safer and easier process. This study aimed to extract S. macrophylla seed oil by using SC-CO2 and investigate the antioxidant, antidiabetic activity and toxicity content of the oil extracted. Antioxidant analysis was performed by using 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity and in vitro antidiabetic analysis was done by using the inhibitory of a-amylase and a-glucosidase to validate antidiabetic activity of S. macrophylla seed oil. Toxicity test of S. macrophylla seed extract was performed using MTT assay on human skin fibroblast cell (HSF 1184). The result showed that S. macrophylla seed extracts at studied concentrations of 10 to 0.0001 mg/mL are non-toxic with cell viability above 80 %. a-amylase and a -glucosidase inhibition (%) of the S. macrophylla seed extracts was 100.0 ± 0.3 % and 4.1 ± 2.0 %. S. macrophylla seed extract was proven to have promising antidiabetic activity to act as an alternative to the commercial antidiabetic drugs.