The research used an artificial neural network (ANN) to examine optimum extraction conditions and phytochemical contents of Luffa cylindrica seed oil. The oil yield was predicted using an artificial neural network. The performance of the ANN and response surface methodology models was compared. The optimum extraction yielded 7.567% oil yield, 185.676 mg/l phenol, and 45.087 mg/l terpineol at 75.57 °C extraction temperature, 5.77 h extraction time, and 10.68 g/mol n-hexane concentration, respectively. These data show that the oil output is poor but has a significant phenol and terpenoid content that may be employed in pharmaceutical sectors. The FT-IR analysis of Luffa cylindrica seed oil revealed a high level of unsaturated hydrocarbons and esters, making the oil appropriate for using in the paint industry and creating cosmetics.