Ketoconazole and Clindamycin are widely used antifungal and antibacterial agents, respectively, and are frequently combined in topical and intravaginal formulations for the treatment of mixed fungal and bacterial infections. Ensuring the quality, safety, and efficacy of such formulations requires reliable and validated analytical methods. The present review critically summarizes the analytical techniques reported for the quantification of Ketoconazole and Clindamycin in bulk drugs, pharmaceutical formulations, and biological matrices. Various spectroscopic methods, including UV and visible spectrophotometry, as well as chromatographic techniques such as RP-HPLC, HPTLC, UPLC, and LC–MS/MS, are discussed with respect to their methodological conditions, sensitivity, and applicability. Special emphasis is placed on stability-indicating chromatographic methods developed in accordance with ICH guidelines, including forced degradation studies. The review also highlights the advantages and limitations of existing methods and identifies the lack of a validated stability-indicating RP-HPLC method for the simultaneous estimation of Ketoconazole and Clindamycin in combined dosage forms. This analytical gap underscores the need for the development of a simple, robust, and regulatory-compliant method suitable for routine quality control and stability studies.