Helicteres hirsuta Lour. (H. hirsuta L.) has been used as a traditional medicine for treatment of various ailments such as malaria and diabetes in Southeast Asian countries. This study aimed to optimize the conventional extraction conditions for obtaining the highest levels of phenolics, flavonoids, and antioxidant activities within H. hirsuta L. using response surface methodology. The Box–Behnken design was employed to evaluate the effects of extraction time, temperature, and the sample‐to‐solvent ratio on bioactive compound yield and antioxidant capacity of H. hirsuta L. The results indicated that the sample‐to‐solvent ratio had the strongest impact on bioactive compounds and antioxidant power of H. hirsuta L. and revealed the optimum extraction conditions to include temperature of 60 °C, time of 35 min at the sample‐to‐solvent ratio of 1 : 100 g/mL using 40% (v/v) methanol as the solvent. Under these conditions, the highest levels of total phenolic content and total flavonoid content were 16.87 mg GAE/g and 17.55 mg CE/g, respectively, significantly higher than the values obtained using water as the solvent. When preparing powered crude extract from H. hirsuta L., the ratio of 3 : 100 (g/mL) was suggested for the saving of 67% of solvent volume and energy required for solvent removal, as similar total phenolic content and total flavonoid content yield (86–87%) as well as antioxidant activities were obtained in comparison with the ratio of 1 : 100 (g/mL). © 2017 Curtin University of Technology and John Wiley & Sons, Ltd.