Naringenin is a bioactive flavanone containing antioxidative, anti-inflammatory, and anticarcinogenic properties. The inhibitory effects oil hyaluronidase of naringenin and its novel derivatives were evaluated. Among these flavonoids at 200 μM concentration, 7-O-butyl naringenin had the highest inhibitory effect oil hyaluronidase with 44.84%. In addition, For naringenin at concentrations of 0, 150, and 190 μM, the apparent Michaelis constants (∧appK∧m) were calculated to be 0.60±0.02, 0.43±0.02, and 0.41±0.01 mg/mL of substrate, respectively; for 7-O-butyl naringenin at 0, 20, and 30 μM concentrations, those were 0.44±0.03 and 0.27±0.03 mg/mL, respectively. The V∧max values at 150 and 190 μM naringenin were 0.59±0.02 and 0.56±0.01 mg/mL/min, respectively; and those at 20 and 30 μM 7-O-butyl naringenin were 0.50±0.02 and 0.33±0.02 mg/mL/min, respectively. However, the slopes of each inhibitory reaction were not significantly different. Therefore, naringenin and 7-O-butyl naringenin were shown to be uncompetitive inhibitors. These results demonstrate the potential use of 7-O-butyl naringenin as all anti-inflammatory substance.