Background Corticosteroids are considered the most effective medication to control chronic rhinosinusitis with nasal polyps (CRSwNP); however, the studies of systemic corticosteroids in this field are relatively few and meta-analyses are lacking. Objective We aimed to systematically review the efficacy and safety of systemic corticosteroids for patients with CRSwNP via meta-analysis. Methods Data were extracted from relevant and appropriate randomized controlled trials (RCTs) of systemic corticosteroids for patients with CRSwNP from PubMed, MEDLINE, Ovid, Embase, the Cochrane Central Register of Controlled Trials, and Google Scholar. Efficacy was assessed based on clinical outcomes, while safety was assessed based on adverse events (AEs). Results A total of 337 relevant publications were identified, of which 7 RCTs including 414 participants were included in the meta-analysis. Compared to placebos or nonsteroid treatments, systemic corticosteroids significantly improved nasal obstruction scores standardized mean difference (SMD -2.81; 95% confidence interval [CI], -4.68 to -0.95; P = .003), reduced the nasal polyp size (SMD -4.76; 95% CI, -6.99 to -2.52; P < .0001), and improved peak nasal inspiratory flow (PNIF) (SMD 42.39; 95% CI, 28.95 to 55.84; P < .00001). The high-dose (more than or equal to 50 mg/day prednisone) and low-dose subgroups (less than 50 mg/day prednisone) experienced similar benefits. However, insomnia and gastrointestinal disturbances were noted more frequently in patients treated with high doses of prednisone. Other AEs were infrequent and were not significantly different between the subgroups. Conclusion Systemic corticosteroids provide significant improvements in nasal symptoms and PNIF as well as a reduction in nasal polyp size for patients with CRSwNP. Prednisone doses less than 50 mg/day were recommended when the efficacy of oral corticosteroids in CRSwNP was balanced against potential adverse effects.