Chronic central serous chorioretinopathy (CSC) usually demonstrates frequent recurrence, diffuse leakage and persistent subretinal fluid, which cannot be absorbed, thus lead to photoreceptor damage and poor visual acuity. As glucocorticoids have been implicated in the pathogenesis of chronic CSC, various anti-glucocorticoids oral drugs were used in the clinic to promote retinal fluid absorption and reduce the central retinal thickness of the macula and improve the vision outcomes. In addition, the 5α-reductase-specific inhibitor finasteride, the P450-3A4 inducer rifampicin, circadian rhythmic regulator melatonin, and systemic anti-inflammatory drug methotrexate have also been put into clinical trials for chronic CSC, and achieved certain effects. However, most of the clinical studies on these oral drugs were case reports, but not multi-center randomized clinical trials. The long-term effects of these oral drugs need to be observed and studied further.