A series of nopinone thiazolidazone drivatives were obtained from nopinone by aldol condensation, acylhydration and cyclization, therein nopinone was obtained from -piene by xidation reactions. All the target compounds were structurally characterized by 1H NMR, 13C NMR and HR-MS, and the antibacterial activitesof these compounds against Staphylococcus aureus, Candida albicans and Klebsiella pneumoniawereinvestigated. The results showed that 2-{2-{6,6-dimethyl-3-(4-nitrobenzylidene)bicyclo[3.1.1]heptan-2-ylidene}hydrazinyl}-4-(4-fluorophenyl)thiazole (Ⅲe), 4-{2-{2-{6,6-dimethyl-3-(-4-nitrobenzylidene)bicyclo[3.1.1]heptan-2-ylidene}hydrazinyl}thiazol-4-yl}phenol (Ⅲf), 2-{2-{3-(4-fluorobenzylidene)-6,6-dimethylbicyclo[3.1.1]heptan-2-ylidene}hydrazinyl}-4-phenylthiazole (Ⅲg), 2-{2-{6,6-dimethyl-3-(4-methylbenzylidene)bicyclo[3.1.1]heptan-2-ylidene}hydrazinyl}-4-phenylthiazole (Ⅲj) had significant inhibitory effect on staphylococcus aureus, and the minimum inhibitory mass concentration was 3.51 μg/L, 0.88 μg/L, 7.03 μg/L and 3.52 μg/L, respectively; 4-{2-{2-(3-benzylidene-6,6-dimethylbicyclo[3.1.1]heptan-2-ylidene)hydrazinyl}thiazol-4-yl}phenol (Ⅲc) had good inhibitory activity on Candida albicans, and the minimum inhibitory mass concentration was 28.12 μg/L. However, all the target compounds had no significant inhibitory effect on Klebsiella pneumoniae. It was indicated that the difference of the substituent groups R1 and R2 leaded different inhibiting activities of the target compound to Staphylococcus aureus from the structure-activity relationship. When R1 is a strong electron-withdrawing group, the antibacterial activity of the compound significantly improved, especially, the inhibitory effect of compound Ⅲf to Staphylococcus aureus is comparable to that of kanamycin sulfate, which has potential development value.