Although previous studies have investigated the safety and efficacy characteristics of oral drugs in patients with premature ejaculation (PE), the available results remained inconsistent. Hence, this article was conducted to comprehensively compare the effectiveness of oral drugs and several relevant complications in patients with PE. Relevant researches were comprehensively searching from the databases PubMed, EMBASE, and Web of Science, up to May 1st, 2018. The pooled standard mean difference (SMD) or odds ratios (ORs) with 95% Credible interval (CrI) was respectively utilized to evaluate the safety and efficacy of oral drugs in PE. A total of 25 relevant research were ultimately included in this network meta-analysis. PE oral drugs mainly included serotonin reuptake inhibitors (SSRIs) and phosphodiesterase type 5 inhibitors (PDE5i). Our results successfully shed light on the efficacy differences of oral drugs for the treatment of PE. The cumulative rank probability of IELT at 4-6 weeks from best to worst was SSRIs + PDE5i, PDE5i, and other SSRIs alone. In addition, this meta-analysis also showed fluoxetine 20 mg, dapoxetine 60 mg, PDE5i, and SSRIs + PDE5i had a higher, whereas other SSRIs alone had a relatively lower incidence rate of clinically relevant complications. In summary, our results showed that the usage of PDE5i only or in combination with SSRIs might be stronger than SSRIs alone in the efficacy of PE oral drugs. Nevertheless, it also has a problem about the side effects of PDE5i including gastrointestinal or central nervous systems complications, which prevents it as the first-line treatment drug. Despite the development of some promising new therapeutic options, SSRIs remained as the first line of therapeutic PE oral drug through a synthetical consideration at present.