Various disinfecting agents showing variable success in disinfecting polymethyl methacrylate (PMMA) are available. The aim of our study was to evaluate the antifungal efficacy of sodium perborate (denture cleaning tablet-DC), microwave irradiation, and their combination for eradicating candida albicans (C. albicans) from polymethyl methacrylate (PMMA) denture base polymer. One hundred and sixty-eight PMMA resin specimens (30 × 30 × 15 mm) were divided into four groups, including control (no disinfection), microwave disinfection in distilled water (MW-DW), sodium perborate with distilled water (DC-DW), and a combination of MW-DC-DW (n = 10). Biofilms of C. albicans were cultured on the PMMA resin denture base specimens for 96 h. The samples were exposed to three different antifungal regimes, i.e., MW, denture cleaning agent-sodium perborate (DC) and DW, and a combination of MW-DC-DW for 1 to 5 min. Scanning electron microscopy (SEM) was performed to evaluate colony formation. The colony-forming units (CFU) among the experimental groups were assessed using ANOVA, a Kruskal–Wallis test, and a Mann–Whitney test. The mean CFU values were compared with the control for each disinfecting regime at 96 h growth time. For MW-DC-DW, the CFU were significantly low at 2 and 3 min of exposure when compared with the control (DW) (p < 0.05). For the MW-DW treated group, the CFU were significantly low at 3 min of exposure when compared with the control (DW) (p < 0.05). It was also found that for DC-DW, the CFU were significantly low at 5 minutes when compared with the control specimens (DW) (p < 0.05). Microwave disinfection in combination with sodium perborate is a more effective disinfecting regime against C. albicans than that of microwave disinfection and sodium perborate alone.