Dodonaea viscosa has long been recognized for its medicinal value, yet a comprehensive understanding of its phytochemical composition and bioactivity remains limited. In this study, a flavonoid-enriched fraction from D. viscosa leaves was investigated by LC-ESI-MS analysis, revealing six phenolic acids and their derivatives alongside sixteen flavonoids, primarily flavones and flavonols. Quantitative analysis confirmed high levels of flavones and flavonols (2518.6 ± 0.13 mg rutin equivalent/100 g extract), while flavanones and dihydroflavonols were present at significantly lower concentrations (401.2 ± 0.11 mg naringenin equivalent/100 g extract). The extract demonstrated potent antioxidant activity, with DPPH scavenging values of 58.36 ± 18, 76.85 ± 13, and 89.75 ± 19%, and ABTS scavenging values of 69.56 ± 0.06, 76.42 ± 0.10, and 84.28 ± 0.07% at concentrations of 10, 50, and 100 μg/mL, respectively. It also exhibited strong dual inhibitory effects against COX-2 (IC₅₀ = 38.21 μg/mL) and 5-LOX (IC₅₀ = 40.72 μg/mL), comparable to indomethacin (IC₅₀ = 33.03 μg/mL) and zileuton (IC₅₀ = 33.41 μg/mL). Mechanistic insights from tandem mass spectrometry and molecular docking further confirmed key interactions responsible for these bioactivities. Collectively, these findings underscore the therapeutic potential of D. viscosa as a natural source of multifunctional bioactive compounds suitable for pharmaceutical and nutraceutical applications. Molecular docking further validated the strong binding affinities of the major flavonoids, with isokaempferide showing particularly stable interactions with COX-2, 5-LOX, and NAD(P)H oxidase. MM-GBSA and hydrogen bond analyses highlighted key residues involved in target inhibition, reinforcing the experimental findings and supporting the potential of D. viscosa flavonoids as promising multifunctional therapeutic leads.