Occurrence of denture stomatitis and prosthesis breakage are common problems faced by elderly people wearing removable dentures. To overcome this, several attempts are made to improve the denture material by addition of antimicrobials without compromising original properties. The aim of the study was to evaluate flexural strength and microhardness of self-cured polymethyl methacrylate (PMMA) denture base resin after addition of Vaccinium macrocarpon (commonly called as cranberry), extract as antimicrobial, at varying proportions. Experimental in vitro study. Frozen cranberry fruits were subjected to extraction process in the presence of aqueous solvents. Lyophilized extract was added in proportions of 0, 0.5, 1.0, 1.5, and 2.0 dry wt/wt % into polymer of self-cure PMMA denture base resin. Based on cranberry inclusion, the study comprised one control (0%) and four test groups (0.5%-2%) with total of 100 samples. A three-point bending test for flexural strength was done for fifty study samples (n = 10). Surface of fractured samples was analyzed using a scanning electron microscope (SEM). Microhardness was determined using Vickers hardness test. One-way statistical ANOVA test was done to find the difference between groups, followed by Tukey's post hoc test for multiple pairwise comparison. Flexural strength ranged from 66.80 to 69.28 MPa, and a statistically insignificant difference was observed between groups (P > 0.05). SEM evaluation showed uniformly dispersed strands of cranberry extract in PMMA matrix. With higher concentration, less voids were seen. Vickers microhardness value significantly decreased from 15.96 in the control group to 14.57 with 2% cranberry addition (P < 0.05). Incorporation of cranberry extract into self-cure PMMA denture base resin, up to 2 dry wt %, did not decline the flexural strength. However, there was a significant decrease in Vickers microhardness values when compared against the control group (0% cranberry inclusion).