Anesthesia has been thought to impact cognitive function in the elderly, although the exact pathophysiology remains uncertain. This systematic review aimed to analyze the impact of ketamine and propofol on cognitive function in elderly patients. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, a comprehensive search was conducted across PubMed/Medline, Cochrane Central Register of Controlled Trials (CENTRAL), Europe PMC, ScienceDirect, ClinicalTrials.gov, and EBSCO Open Dissertations on November 17, 2024. After screening, the methodological quality of the included studies was assessed using the Cochrane Risk-of-Bias-2 Tool and the Newcastle Ottawa Scale. Studies were included if they focused on patients aged 60 and older, encompassing 3,149 participants across 19 studies, predominantly randomized controlled trials. Key outcomes assessed included postoperative cognitive dysfunction (POCD) and postoperative delirium (POD). Results indicated that many studies found no significant differences in cognitive outcomes between certain anesthetic drugs. However, ketamine was likely associated with an increased risk of POCD, similar to propofol, when compared to remimazolam and dexmedetomidine. Notably, ketofol reduced POD incidence compared to placebo, while higher propofol doses were linked to an increased incidence, and severity of hypoactive POD. The most evident finding was that propofol attenuated POCD compared to inhaled anesthetic agents. Given this, it is crucial for clinicians to carefully consider anesthetic choices for elderly patients. Future research should focus on larger multicenter trials to further validate these results and explore the long-term cognitive effects of various anesthetic agents.