The use of medicinal plants has been of interest since the distant past. Ocimum sanctum (OS) plant has significant therapeutic properties due to its various bioactive compounds. Among the important compounds, oleanolic acid, with many therapeutic uses such as ant-cancer, antioxidant, and diabetes treatment, is of interest. The maximum extraction of the compounds has always required the optimization of the extraction process. Different factors, including solvent-to-solid ratio, extraction time, solvent composition, and particle size, are involved in the extraction of the oleanolic acid process. Using the response surface methodology (RSM) to design the experiments and investigate the effects of various parameters on extraction efficiency is one of the best optimization techniques. Fuzzy logic (FL) is also used to investigate uncertainties. In this chapter, the studies conducted to optimize the extraction process of oleanolic acid from Ocimum sanctum using RSM and FL are explained in detail. This hybrid approach identifies the optimal conditions for extraction and demonstrates the interaction between different parameters.