This research synthesizes, characterizes, and applies Cissus quadrangularis phytosomes to transdermal patches for arthritis. Phytosomes were prepared from lipoid P 30 and crude C. quadrangularis ethanolic extract and characterized by optical microscopy, SPR, ATR-FTIR, XRD, FE-SEM, HRTEM, and Zetasizer Nano ZS. The evaporating solvent created transdermal patches with different polymer-phytosome ratios. To ensure the safety of the phytosomal formulation, its acute toxicity was investigated. In Wistar Albino rats, carrageenan intradermally caused arthritis was used to test the anti-arthritis activity of transdermal patches. Four groups of rats were tested: control, commercial transdermal patch, C. quadrangularis phytosome patch, and arthritic control. The C. quadrangularis phytosome transdermal patch reduced inflammation compared to that in the arthritic control group. Statistical analysis was performed using Prism 5. This study suggests C. quadrangularis phytosome transdermal patches may be used to treat arthritis, paving the way for future research. Microscopic investigation revealed the phytosome structural shape, content, and delivery system applications. UV spectroscopy revealed 15.044 OD220, indicating the presence of aromatic or conjugated structures. FT-IR spectroscopy revealed O-H stretching vibrations at 3842.20 cm^-1 in bioactive compounds. XRD analysis showed a phytosome crystallinity of 49.67 %. Particle analysis indicated good stability and dispersion with 86.29 an average particle size and -20.9 mV zeta potential. FESEM and HR-TEM exhibited nanoscale homogeneity and morphology. In acute toxicity testing of female rats, phytosomes were harmless. The phytosome transdermal patch reduced the paw volume and thickness of Wistar rats, similar to commercial anti-arthritis medications. Histopathological examination confirmed the anti-inflammatory effects of transdermal patches. Statistical analysis demonstrated significant improvements across the experimental groups, proving treatment efficacy. LC-MS revealed C. quadrangularis substances with anti-rheumatic properties. C. quadrangularis phytosomes may improve arthritis treatment via a holistic approach.