Swietenia macrophylla contain multiple bioactive compounds with anti-inflammatory, anti-diabetic, anti-tumour and antioxidant properties. Standardised extraction techniques with optimum oil yield recovery are needed as compared to conventional method that requires huge volume of solvent and longer extraction time. S. macrophylla seed was extracted by using microwave-assisted extraction (MAE) technique to improve the oil yield and phytochemical properties at different processing parameters. A comparison study on oil yield, bioactive compounds, antioxidant and antidiabetic analysis was conducted with other methods namely supercritical carbon dioxide extraction (SC-CO2), and soxhlet extraction (SE) methods at optimum extraction conditions. The result showed that 43.69 ± 0.09 w/w % oil yield was obtained at optimal condition of 6 min irradiation time, solvent-to-solid ratio of 26 mL solvent/g solid and 460 W microwave power with oleic acid as the major fatty acid component from MAE extraction. The seed oil extracted using MAE exhibited the highest total phenolic content and antioxidant properties as compared to the SC-CO2 and SE methods. S. macrophylla seed oil demonstrated potent inhibition of the α-amylase enzyme, suggesting potential antidiabetic properties. The extracts also showed excellent inhibition of Escherichia coli and Bacillus subtilis. These findings prove that S. macrophylla seed oil extracted using MAE can provide better quantity and quality oil in a shorter time compared to the SC-CO2 and SE methods.