Response surface methodology (RSM) was applied to predict optimum conditions for microwave-assisted extraction (MAE) of total limonoid (TL) and antioxidant potential investigation from Trichilia roka (Chiov) root bark. A central composite design methodology (CCDM) was used to minor the effect of the independent variables such as irradiation time (X1), irradiation power (X2), liquid-to-solid ratio (X3) and methanol polarity (X4) on the dependent variables namely total limonoid (TL), total polyphenol (TPP), DPPH radical scavenging activity and β-carotene antioxidant activity (AOA). The optimal combined conditions for extracting maximum TL (116 ​mg RUBE/gDW), TPP (12.5 ​g GAE/100gDW) and antioxidant activity (DPPH 90.1%; AOA 90.5%) were irradiation time 80 ​s, irradiation power 600 ​W, liquid to solid ratio 0.6/20 ​mL/g and methanol concentration 40%. All the factors significantly (p ​< ​0.01) influenced the responses, the variations from the independent variables corresponding significantly to the predicted polynomial model and the maximum values estimated at the predicted optimal condition were in good agreement with experimental value. In conclusion MAE of antioxidant compounds from Trichilia roka (Chiov) root bark is highly influenced by equipment parameters of functioning (microwave irradiation time and power) as well as the solvent (liquid to solid ratio and methanol concentration), following a second degree polynomial model. •Identification of optimal range of extraction operational conditions for microwave extraction process of total limonoids content from Trichilia roka root bark.•The optimal conditions for extracting by microwave assisted extraction the maximum limonoids compounds from Trichilia roka (Meliaceae).•Evaluation of antioxidant activity using DPPH radical scavenging and oxidative degradation of β-carotene.•Description of one strategy to optimize that extraction of limonoid and polyphenol compounds using response surface methodology.