OBJECTIVE: The antimicrobial efficacy of cranberry (CA) against oral infections was well evidenced. Influence of cranberry on the mechanical properties of heat-activated polymethyl methacrylate (HA-PMMA) denture base resin (DBR) is unexplored till date and is significant for a better understanding of the reinforcement. This study aimed to evaluate the flexural strength (FS), impact strength (IS), and surface microhardness (VHN) of heat-cure PMMA DBR reinforced with varying concentrations of Vaccinium macrocarpon (cranberry) extract. MATERIAL AND METHODS: A total of 150 samples were categorized into five groups (n = 10) by weight percentage of 0, 0.5, 1.0, 1.5, and 2.0 cranberry extract added into HA-PMMA polymer after the performance of antimicrobial efficacy testing of CA. Three-point bending test for FT, Izod impact testing for IS, and Vickers microhardness test were performed. Fractured sample surface was characterized by a high-resolution scanning electron microscope (HR-SEM). Raw data were statistically analyzed with one-way ANOVA and post hoc Bonferroni test. RESULTS: A significant improvement in flexural strength of 76.88 ± 0.73 MPa, impact strength of 6.66 ± 0.24 kJ/m CONCLUSIONS: Addition of up to 2 wt.% cranberry improved the FS, IS, and VHN on comparison to 0 wt.% control HA-PMMA.