The goal of the current study was to create an ethosomal gel of CXB to treat rheumatoid arthritis. Different amounts of lipoid S100 (50 mg–200 mg), ethanol (20–50%), and water were used to create CXB ethosomes. The drug encapsulation efficiency, vesicle size, PDI, surface charge, and shape of the produced nanovesicles were identified. The optimisedethosomal formulation exhibited a zeta potential of -31.1 mV, a particle size of 161±0.01 nm, a polydispersity index (PDI) of 0.259, an entrapment efficiency of 89.21%, and a drug release of 97.87% in a 24-hour period. The optimised formulation's TEM investigation revealed somewhat smooth spherical formations. The drug's hydroalcoholic solution could only pass up to 75.5 µm, however ethosomes could readily infiltrate deeper dermal layers (up to 104.3 µm), according to Confocal laser scanning microscopy. Additionally, the optimisedethosomal formulation was added to a 1% carbopol 934 gel basis and further optimised, resulting in a transdermal flux that was discovered to be roughly ten times greater than that of the hydroethanolic solution. The ethosomal gel was created with success and has demonstrated that it could be a viable alternative to traditional rheumatoid arthritis treatments.