Lycium barbarum, known as wolfberry or goji berry, is consumed by humans as a medicine and a food homology product. Conventionally grown wolfberry is often treated extensively with pesticides, which could pose a hazard to humans. Here, the degradation dynamics of dinotefuran and its 2 metabolites (1-methyl-3-(tetrahydro-3-furylmethyl) urea (UF) and 1-methyl-3-(tetrahydro-3-furylmethyl) guanidine (DN)), during wolfberry cultivation and processing was investigated. The half-life (T1/2) of dinotefuran was 11.36 and 9.76 days, respectively, under the recommended dosage and double the recommended dosage. During the oven and sun drying processes, processing factors (PFs) of dinotefuran were 1.07−1.34, implying the enrichment of pesticide residues. Decoction process made the removal rate of dinotefuran reach 87.48%, which is higher than that of the brewing process (14.7%), while dinotefuran remained in the wine with high ethanol content in the alcohol soaking process. The hazard quotient (HQ) of dinotefuran, as determined via dietary risk assessment combined with PFs, was < 1, indicating an acceptable risk for human consumption. Bioaccessibility of dinotefuran in the three digestive stages were intestinal (18.20%−88.08%) > gastric (5.45%−86.72%) > oral (23.18%) via in vitro simulated digestive system. These findings provide scientific evidence for reasonable application and risk assessment of dinotefuran residues in wolfberry.