ObjectiveTo systematically review the efficacy and safety of different drugs for the treatment of intermittent claudication in patients with peripheral arterial disease. MethodsThe PubMed, Scopus, EMbase, The Cochrane Library, Web of Science, CNKI, WanFang Data and VIP databases were searched to collect randomized controlled trials (RCTs) of intermittent claudication due to peripheral arterial disease from database inception to December 31st, 2021. Two researchers independently screened the literature, extracted data, and assessed the risk of bias of the included studies. Network meta-analysis was then performed using Stata 16.0 software. ResultsA total of 36 studies were included, which involved vasodilators (i.e., cilostazol), lipid-lowering agents (i.e., atorvastatin), antiplatelet drugs (i.e., sarpogrelate), and other types of medicine (i.e., L-carnitine and allopurinol). The results of meta-analysis showed that the effects of simvastatin, bencyclane, and ramipril were superior to cilostazol and other drugs in improving PFWD, among which bencyclane was the most efficient. Besides, simvastatin and ramipril were also superior to cilostazol and other drugs in improving MWD (P<0.05). However, there was no statistically significant difference between cilostazol and other drugs (P>0.05). In terms of adverse events, iloprost was inferior to other drugs, while sulodexide was better tolerated. ConclusionBencyclane is a preferred choice to improve PFWD for the treatment of IC due to PAD, simvastatin and ramipril to improve MWD; however, their safety is poor. Overall, sulodexide and L-carnitine are ideal medicines for IC. Due to the limited quality and quantity of the included studies, more high-quality studies are needed to verify the above conclusion.