Background <p>Anorexia nervosa (AN) is a complex psychiatric disorder marked by extreme caloric restriction, intense fear of weight gain, and distorted body image perception. Not only influence physical health, but it also creates serious psychological burdens. Treatment of AN is especially daunting due to its multi-dimensional nature. Recent research indicates that a pharmacological approach, such as the prescription of atypical antipsychotics like Olanzapine, may help treat both the nutritional deficiency and psychological distress related to the disorder. By allowing an individual gain weight and potentially reducing comorbid depression and anxiety, Olanzapine can be a valuable add-on to standard treatments.</p> Aim <p>This study aims to investigate the effectiveness of Olanzapine in causing weight gain among anorexia nervosa patients. Based on comparisons of results in a number of clinical trials, the study aims at establishing the effect of Olanzapine on weight restoration and investigating any accompanying shift in the psychological state of the patients.</p> Method <p>A comprehensive literature search was performed on Medline, ClinicalTrials.gov, Scopus, and the Cochrane Database of Systematic Reviews for all records from the earliest date available through to August 22, 2024. Randomized controlled trials of olanzapine treatment in anorexia nervosa were included. Studies were screened, and data were extracted. Risk of bias was assessed with the Cochrane risk-of-bias tool. Records for meta-analysis were combined in a random-effects model to calculate effect sizes, and heterogeneity was quantified with the I² statistic.</p> Result <p>207 records were found, 159 of which were excluded after title and abstract screening. After full-text review, seven RCTs were found. These trials involving 152 patients assessed the impact of olanzapine on weight gain in anorexia nervosa. Meta-analysis of 4 studies (91 patients) showed a mean difference in BMI of 1.68&#xa0;kg/m² (95% CI: 0.82, 4.18) in favor of olanzapine but not statistically significant (<i>p</i> = 0.19), with high heterogeneity (I² = 94%). Sensitivity analysis reduced the heterogeneity to 28% but not the effect size.</p> Conclusion <p>Although olanzapine showed a numerically greater weight gain compared to control conditions, the pooled effect did not reach statistical significance and was associated with substantial heterogeneity. Therefore, current evidence remains inconclusive. Olanzapine may be considered in selected cases, particularly where psychological comorbidities are prominent, but larger and methodologically robust trials are needed before routine clinical use can be recommended.</p> Clinical trial number <p>Not Applicable.</p>