This study aimed to determine the chemical functional groups and cytotoxicity level of denture base resin (DBR) material reinforced with oil palm based microcrystalline cellulose (MCC) at different concentrations. Three MCC-reinforced polymethyl methacrylate (PMMA) specimens were compared with conventional and commercially available high-impact PMMA. The test groups were represented by adding various MCC and acrylic polymer concentrations. Fourier Transform Infrared Spectroscopy (FTIR) was conducted to compare the chemical structure of the specimen groups. Cytotoxicity was evaluated by filter diffusion test. Extracts from study groups were tested using the MTT assay protocol for cell viability and proliferation with normal human oral fibroblast (NHOF). The FTIR analysis showed that good bonding between MCC OPEFB and PMMA as the functional group strength was reliable in cellulose-treated PMMA. The analysis also confirmed high integrity and successful grafting between the two. Cell viability assays showed that exposure of NHOF to polymer-MCC mixture eluates did not promote cell death or considerable toxic impacts. Suitably processed oil palm-based MCC-reinforced DBR can improve the bonding and integrity of the composite material without compromising its biocompatibility leading to the development of reinforced DBR with enhanced microstructural and chemical properties.