This study aims to evaluate the effect of extraction solvent type on the physicochemical properties and bioactive compounds of Actinostemma lobatum Maxim. kernel oil for two successive harvest years. Oils were extracted using the bio-based solvent 2-methyltetrahydrofuran (2-MeTHF) and conventional petroleum-derived solvents (n-hexane and 2-methylpentane). Results indicated that 2-MeTHF achieved significantly higher oil yields (27.60% in 2021 and 29.77% in 2022) compared to n-hexane and 2-methylpentane. Unfortunately, 2-MeTHF-extracted oils exhibited greater susceptibility to oxidation, displaying elevated levels of primary and secondary oxidation products relative to other solvents. Meanwhile, 2-methylpentane-extracted oil showed a relatively high oxidative stability index. In addition, differential scanning calorimetry results also aligned with the oxidative status. Further variance analysis revealed that the harvest year exerted a more pronounced impact on fatty acid and triacylglycerol profiles than the solvent type. Additionally, tocopherols and tocotrienols were abundant, with β- and δ-tocopherols predominating. 2-MeTHF-extracted oils harvested in 2022 contained the highest total tocols (1118.83 mg/kg) among all samples. Also, phytosterols were detected, with β-sitosterol constituting the predominant compound. Furthermore, the 2-MeTHF-extracted oils contained higher β-carotene contents compared to other samples. These above findings concluded that 2-MeTHF is a good alternative to conventional solvents for extracting of A. lobatum kernel oil.