The aim of the present research is to develop a topical Cubosomal gel formulation of Crisaborole, an anti-inflammatory non-steroidal phosphodiesterase 4 inhibitor currently being investigated for its potential in treating atopic dermatitis. Pre-formulation studies included determination of melting point, DSC (differential scanning calorimetry), FT-IR spectroscopic analysis, wavelength determination, calibration curve establishment, and drug-excipient compatibility studies. Top-down techniques were employed to prepare cubosomes. Thirteen different formulations (C1-C13) were developed to optimize parameters such as particle size, size distribution, zeta potential, and entrapment efficiency. The physical characteristics including appearance, pH, viscosity, spreadability, and Transmission Electron Microscope (TEM) analysis were evaluated. In-vitro drug release studies were conducted for the crisaborole-loaded cubosomal gel formulation (CRB-C1), which utilized Glyceryl monooleate as the lipid, Poloxamer 407 as the stabilizer, and Carbopol 934 as the gel base. CRB-C1 showed optimized parameters with a particle size of 135.70 ± 0.58 nm, polydispersity index (PDI) of 0.249 ± 0.01, zeta potential (ZP) of -21.50 ± 4.25 mV, and entrapment efficiency of 91.95 ± 0.50%. The developed cubosomal gel formulation (C1) exhibited clarity without any aggregates, indicating excellent homogeneity. In-vitro drug release studies demonstrated favorable release kinetics for formulation C1.