The aim of this study was to assess the efficacies and toxicities of immunosuppressive treatments for lupus nephritis (LN) versus cyclophosphamide (CYC). A meta-analysis was performed to determine treatment efficacy and toxicity outcomes between mycophenolate mofetil (MMF) and CYC induction therapies, between MMF and azathioprine (AZA) as maintenance therapies, and between low-dose intravenous (IV) CYC and high-dose IV CYC therapy. Ten randomized controlled trials (RCTs) were included in the meta-analysis. In terms of induction therapies, MMF did not increase complete remission or partial remission rates as compared with CYC. However, the relative risks (RRs) of amenorrhea and leukopenia tended to be lower in the MMF group than in the CYC group. Meta-analysis of MMF versus AZA as a maintenance therapy showed no difference between the two groups in terms of response rates or the risk of developing end-stage renal disease. Low-dose IV CYC therapy had lower relapse rates than high-dose IV CYC therapy (RR 0.465, 95% confidence interval [CI] 0.261-0.830, p-value 0.010), and was associated with a lower infection risk (RR 0.688, 95% CI 0.523-0.905, p-value 0.008). In conclusion, MMF was found to be as effective as CYC and tended to have a better safety profile as an induction therapy for LN than CYC.