Lycium ruthenicum is rich in health-promoting anthocyanins and other flavonoids, however the effects of blue light (BL) and NaCl on their biosynthesis remained poorly understood. UPLC-MS/MS and chemometrics were utilized to investigate individual and combined effects of BL and NaCl treatments on flavonoids in detached L. ruthenicum leaves. BL significantly increased total anthocyanin content to 1.35 units·g⁻¹ FW, 150 mM NaCl raised it to 2.64, and their combination further enhanced anthocyanin accumulation to 3.40. Comprehensive metabolomic profiling identified 495 flavonoids across different treatments. PCA and OPLS-DA revealed that BL and NaCl activated specific flavonoid biosynthesis pathways. BL preferentially enhanced quercetin derivatives and cyanidin 3-O-(6-p-coumaroyl)glucoside accumulation, whereas WL-NaCl markedly promoted the conversion of naringenin to eriodictyol, leading to dihydromyricetin biosynthesis. Combined treatments significantly stimulated the transformation of dihydrokaempferol into dihydromyricetin, and further boosted petunidins accumulation. These findings offered valuable strategies to enhance bioactive compounds production in L. ruthenicum for nutraceutical applications.