This study addresses the growing environmental concerns associated with petroleum-based lubricants by developing high-performance, sustainable biolubricants derived from non-edible karanja oil. Karanja trimethylolpropane esters (KTMPE) were synthesized through a three-step esterification–transesterification process, with FTIR analysis confirming successful conversion to biolubricant-grade esters. To enhance tribological properties, reduced graphene oxide/molybdenum disulfide (rGO/MoS2) hybrid nanoparticles (3:2 mass ratio) were integrated into the biolubricants at concentrations from 0.1 to 1.0 wt.%. Raman spectroscopy, XRD analysis, and TEM imaging verified the structural integrity and successful hybridization of the nanoparticles. Rheological testing revealed consistent Newtonian behavior across all formulations, with nanoparticle addition improving viscosity index and thermal stability. Tribological evaluation using a four-ball tribometer demonstrated that 0.6 wt.% rGO/MoS2 concentration yielded optimal performance, producing marked reductions in friction coefficient and WSD due to improved dispersion stability and robust tribofilm formation. Comparative analysis with synthetic PAO4 confirmed the superior antiwear and friction-reducing capabilities of the enhanced biolubricants. FE-SEM and EDAX analyses further validated protective tribofilm development through the presence of carbon, molybdenum, and sulfur on worn surfaces. An artificial neural network model optimized using Bayesian Regularization identified a 14-neuron architecture as optimal, achieving a correlation coefficient of 0.999698 and a mean squared error of 0.00279. Overall, the results establish rGO/MoS2-enhanced KTMPE biolubricants represent a promising renewable alternative to synthetic oils for automotive lubrication.