<p>The present study aimed to determine the effect of spiritual interventions on hope among patients with chronic diseases. This systematic review and meta-analysis study was conducted based on the PRISMA 2020 guidelines. International databases (PubMed, Web of Science, Scopus, Embase, Science Direct, Google Scholar) and Iranian databases (Magiran, SID) were searched up to September 8, 2025, using the operators “AND” and “OR” without time restrictions. The inclusion criteria consisted of randomized controlled trials or clinical trial studies that examined various spiritual interventions to promote hope in adults with chronic physical illnesses. After removing duplicates, initial and secondary screenings were independently performed by two reviewers, and finally, a total of 18 eligible studies were included. Risk of bias was assessed using the Cochrane tool. A total of 18 studies involving 1410 participants (intervention = 708; control = 707), conducted between 2008 and 2024 across five countries, were included in the review. The interventions consisted of structured spiritual care, religious counseling, self-care education, and prayer. Hope was assessed using validated instruments, including the Herth Hope Index (HHI), the Miller Hope Scale (MHS), and Snyder’s Adult Hope Scale (AHS). The majority of studies reported significant improvements in hope among participants in the intervention groups compared with controls, whereas only one study found nonsignificant results. Overall, the meta-analysis demonstrated a strong and significant effect in favor of the intervention group (Cohen’s d = 1.90, <i>p</i> &lt; 0.001). According to the findings, spiritual interventions effectively enhance hope in patients with chronic physical diseases. These results highlight the importance of integrating spiritual interventions into the care plans of such patients and underscore the need for further research on standardized protocols and long-term outcomes.</p>