The combination of high free fatty acid (FFA) palm oil and non-edible microalgae oil presents a promising avenue for sustainable biodiesel production. Efficient catalyst development and innovative technologies are crucial, particularly for the esterification reaction in feedstock pre-treatment processes. In this study, two novel active pharmaceutical ingredients (API)-based deep eutectic solvents (DESs) were introduced. They derived from p-toluenesulfonic acid monohydrate (PTSA) and benzenesulfonic acid (BZSA) combined with aspirin (ASA), encapsulated within medical capsules for safe handling and storage. These DESs effectively reduce FFA content from 11% to less than 2% under optimum conditions (1 wt.% of DES catalyst dosage, 10:1 methanol-to-oil molar ratio, 60°C esterification reaction temperature and 60 min reaction time). The activation energies of the reaction using ASA:PTSA and ASA:BZSA based DES were determined as 53.11 kJ mol^–1 and 39.20 kJ mol^–1, respectively, according to the pseudo first order reaction rate. Furthermore, FFA to fatty acid methyl ester (FAME) conversion rates remained above 50% for both DESs even after three consecutive recycling runs. The utilisation of API-based DESs enhances catalyst physical properties, recyclability for FFA esterification reactions, underscoring their potential in advancing biodiesel production processes.