BACKGROUND: Selective serotonin reuptake inhibitors are currently the preferred drugs for treating depression, a condition that has become more prevalent in recent years. Fluoxetine is one of the most widely used, but, like other antidepressants, it can cause several systemic and oral adverse effects. This systematic review aimed to analyze the frequency of oral adverse effects of fluoxetine in comparison to other antidepressants. MATERIAL AND METHODS: A systematic review was conducted following PRISMA guidelines. A comprehensive literature search was performed in MEDLINE via PubMed, Scopus, The Cochrane Library, and Web of Science, with no date restrictions, including randomized clinical trials and observational studies. The risk of bias was assessed using the Revised Cochrane Risk-of-Bias Tool for randomized trials. RESULTS: A total of 333 articles were identified. After removing duplicates and applying inclusion criteria, 31 randomized clinical trials were selected for analysis. Fluoxetine was primarily compared with tricyclic antidepressants, SSRIs, serotonin-norepinephrine reuptake inhibitors, and other antidepressants. The most frequently reported oral side effect was dry mouth, with prevalence rates ranging from 2.71% to 52.17%, though it was generally lower than with other antidepressants. Dysgeusia was less frequently reported, with only two studies documenting taste alterations. Oral side effects were primarily assessed through subjective patient reports, and no studies incorporated objective salivary flow measurements. Other adverse effects, such as nausea and vomiting, were commonly mentioned, but their potential oral consequences were not evaluated. CONCLUSIONS: Fluoxetine is associated with oral side effects, with dry mouth being the most frequently reported. However, data on dysgeusia remain limited, highlighting the need for further research to determine its prevalence. Given the potential impact of dry mouth on oral health and quality of life, future studies should incorporate objective salivary measurements and further investigate the clinical implications of these adverse effects.