Abstract Background Synthetic glucocorticoids are widely used among patients suffering from a wide range of diseases. Glucocorticoids are very efficacious, but can be accompanied by neuropsychiatric adverse effects. This systematic review and meta-analysis assesses and quantifies the proportion of different neuropsychiatric adverse effects in patients using synthetic glucocorticoids. Methods Six electronic databases were searched to identify potentially relevant studies. Randomized controlled trials, cohort and cross-sectional studies assessing psychiatric side effects of glucocorticoids measured with validated questionnaires were eligible. Risk of bias was assessed with RoB 2, ROBINS-I, and AXIS appraisal tool. For proportions of neuropsychiatric outcomes, we pooled proportions, and when possible, differences in questionnaire scores between glucocorticoid users and non-users were expressed as standardized mean differences (SMD). Data were pooled in a random-effects logistic regression model. Results We included 49 studies with heterogeneity in study populations, type, dose, and duration of glucocorticoids. For glucocorticoid users, meta-analysis showed a proportion of 22% for depression (95%CI 14%-33%), 11% for mania (95%CI 2%-46%), 8% for anxiety (95%CI 2%-25%), 16% for delirium (95%CI 6%-36%), and 52% for behavioural changes (95%CI 42%-61%). Questionnaire scores for depression (SMD of 0.80 (95%CI 0.35-1.26)), and mania (0.78 (95%CI 0.14-1.42)) were higher than in controls, indicating more depressive and manic symptoms following glucocorticoid use. Conclusions The heterogeneity of glucocorticoid use is reflected in the available studies. Despite this heterogeneity, the proportion of neuropsychiatric adverse effects in glucocorticoid users is high. The most substantial associations with glucocorticoid use were found for depression and mania. Upon starting glucocorticoid treatment, awareness of possible psychiatric side effects is essential. More structured studies on incidence and potential pathways of neuropsychiatric side effects of prescribed glucocorticoids are clearly needed.