Background: Artificial intelligence (AI)–based psychotherapeutic interventions may bring a new and viable approach to expanding psychiatric care. However, evidence of their effectiveness remains scarce. We evaluated the efficacy of AI‐based psychotherapeutic interventions on depressive, anxiety, and stress symptoms at postintervention and follow‐up assessments. Methods: A three‐step comprehensive search via nine electronic databases (PubMed, Embase, CINAHL, Cochrane Library, Scopus, IEEE Xplore, Web of Science, PsycINFO, and ProQuest Dissertations and Theses) was performed. Results: Thirty randomized controlled trials (RCTs) in 31 publications involving 6100 participants from nine countries were included. The majority (79.1%) of trials with intention‐to‐treat analysis but less than half (48.6%) of trials with perprotocol analysis were graded as low risk. Meta‐analyses showed that interventions significantly reduced depressive symptoms at the postintervention assessment ( t = −4.40, p = 0.001) with medium effect size ( g = −0.54, 95% CI: −0.79 to −0.29) and at 6–12 months of assessment ( t = −3.14, p < 0.016) with small effect size ( g = −0.23, 95% CI: −0.40 to −0.06) in comparison with comparators. Our subgroup analyses revealed that the depressed participants had a significantly larger effect size in reducing depressive symptoms than participants with stress and other conditions. At postintervention and follow‐up assessments, we discovered that AI‐based psychotherapeutic interventions did not significantly alter anxiety, stress, and the total scores of depressive, anxiety, and stress symptoms in comparison to comparators. The random‐effects univariate meta‐regression did not identify any significant covariates for depressive and anxiety symptoms at postintervention. The certainty of evidence ranged between moderate and very low. Conclusions: AI‐based psychotherapeutic interventions can be used in addition to usual treatments for reducing depressive symptoms. Well‐designed RCTs with long‐term follow‐up data are warranted. Trial Registration: CRD42022330228