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This application discloses a soluble microneedle composition of a GLP-1R agonist and its preparation method, belonging to the field of biomedical technology. It includes a needle body material and a base material. The needle body material contains a small molecule GLP-1R agonist, a penetration enhancer, and a soluble polymeric backbone material, and may further include pH adjusters, humectants, and stabilizers. The base material is composed of polylactic acid, polylactic acid-glycolic acid copolymer, cross-linked polyhyaluronic acid, cross-linked gelatin, polyvinyl alcohol, polyvinylpyrrolidone, polyvinylpyrrolidone-vinyl acetate copolymer, N-(2-hydroxypropyl)methacrylamide polymer, or combinations thereof. Through injection, centrifugation, and drying, an integrated microneedle structure with mechanical strength and rapid dissolution is formed. It can pierce the stratum corneum of the skin to form microchannels and rapidly dissolve and release oxaliplatin subcutaneously, achieving transdermal delivery, effectively reducing gastrointestinal exposure and first-pass metabolism, and improving drug utilization and medication adherence.