Uranium (U), an essential source for nuclear energy production, poses serious environmental and radiological threat due to its high mobility and long half-life. Uranophane [Ca(UO2)2SiO3(OH)2·5H2O], a secondary U silicate mineral, is known as a solubility-limiting phase in U mining deposits and nuclear waste repositories (controlling U immobilization). However, research on uranophane dissolution, particularly under the influence of organic and inorganic ligands, remains lacking. This study investigates uranophane synthesis and its dissolution at pH 8 through batch experiments using organic ligands (citric acid (CA) and humic acid (HA) at 50–150 ppm) and inorganic ligands (carbonate, nitrate, chloride, and silicate at 10−4 M to 10−6 M). Obtained results suggested that CA and carbonate significantly enhanced U release, reaching 27.6 ppm. Mixed systems containing both organic (50–150 ppm CA) and inorganic (10−4 M carbonate) ligands revealed increased U release, however were less effective than single-ligand systems due to competitive interactions with carbonate dominating U speciation. Visual MINTEQ modeling was used to identify uranyl complex species in the solutions. Dissolution rate and kinetic modeling were determined to predict U release trends. These findings emphasize the role of various ligand types in nature and their impact on U mobility, aiding remediation strategies for contaminated environments.