Mycosis fungoides (MF) and Sézary syndrome (SS) are subtypes of cutaneous T-cell lymphoma with numerous topical and systemic therapies. Early-stage MF can be managed with topical corticosteroids, mechlorethamine, and phototherapy. However, patients are often non-responsive to topical therapies, thus requiring systemic therapies. There are few studies summarizing oral (PO) therapies for MF and SS. We aim to discuss the efficacy and safety of FDA-approved, off-label, and investigational oral therapies for MF and SS. FDA-approved oral therapies include bexarotene and vorinostat, both of which are effective in patients who are recalcitrant to prior topical therapies. Off-label oral therapies include methotrexate, acitretin, and chlorambucil. Methotrexate improves MF lesions in both early-stage and late-stage MF and is effective in erythrodermic MF. A combination of acitretin with phototherapy may lead to better response rates compared to acitretin monotherapy. Chlorambucil is mainly used to treat erythrodermic MF. Investigational oral therapies for MF include tenalisib, duvelisib, cerdulatinib, lenalidomide, bortezomib, and azacytidine, and direct comparison studies between these investigational agents and FDA-approved therapies should be undertaken to better understand their role in the management of MF and SS.