Everyday use of denture cleansers to prevent microbial colonization on dentures can affect the properties of the denture base material. Limited literature is available on the effects of denture cleanser on reinforced resins. This study aimed to evaluate and compare the effect of denture cleanser on the flexural and impact strength of conventional and reinforced heat cure acrylic resins. Materials and Methods: Rectangular shaped specimens were prepared for flexural and impact strength as per ISO 1567. The denture base resins used included conventional, high impact, nylon fiber reinforced and glass fiber reinforced heat cure acrylic resins. They were further categorized into subgroups A and B depending on immersion in distilled water or denture cleanser (3.8% sodium perborate based). The flexural strength and impact strength of specimens were measured. The study design is a observational case-control study. SPSS version 25 statistical analysis software was used, and the STROBE statement checklist was followed. Results: The mean flexural strength was highest for glass fiber reinforced heat cure resin followed by conventional heat cure resin, high impact heat cure resin and nylon reinforced heat cure resin, respectively. The mean impact strength was highest for high impact heat cure resin followed by glass fiber reinforced heat cure resin, conventional heat cure resin, and nylon fiber-reinforced resin respectively. Conclusion: All the denture base resins tested exhibited a decrease in flexural and impact strength following use of a denture cleanser.