Introduction: Matrix metalloproteinase-8 (MMP-8) is considered as one of the most promising diagnostic markers for periodontal disease. Androgen deprivation therapy (ADT) has been correlated with impaired collagen synthesis and an increase in periodontal tissue susceptibility to pathogenic microorganisms. Objective: This study aims to investigate the impact of ADT on salivary MMP-8 level and periodontal parameters, which might be useful in monitoring periodontal disease in prostate cancer patients undergoing ADT. Materials and Methods: A total of 88 subjects were selected and were divided into two groups: Group I included n = 78 PC patients who have been undergoing ADT); Group II included n = 10 healthy individuals. Periodontal parameters such as plaque index (PI), gingival index (GI), periodontal probing depth (PPD), and clinical attachment level (CAL) were examined. The salivary MMP-8 level was estimated by using the sandwich enzyme-linked immunosorbent assay method. Results: Significant differences in mean salivary MMP-8 level were found between PC patients undergoing ADT and healthy individuals. Salivary MMP-8 levels of all individuals were positively correlated with GI, PI, PPD, and CAL. Salivary MMP-8 can distinguish between periodontitis and healthy individuals with an accuracy of about 80%. Conclusion: Salivary MMP-8 levels were found to be higher in prostate cancer patients undergoing ADT compared to healthy individuals.