Novel phenylamino quinazolinone derivatives were synthesized as tyrosinase inhibitors. Compound 9r showed the strongest activity (IC₅₀ = 17.02 µM) versus kojic acid (IC₅₀ = 27.56 µM) and 24.67% antioxidant inhibition at 100 µM. Docking and DFT analyses confirmed favorable binding, stability, and reactivity. Kinetic studies revealed competitive inhibition (Kᵢ = 14.87 µM), and molecular dynamics simulations showed stable 9r–tyrosinase interactions, highlighting 9r as a promising tyrosinase inhibitor candidate.