OBJECTIVE Matrix metalloproteinases (MMPs) play a crucial role in the pathogenesis of dental caries, collapse of adhesive interface, and chemical erosion of teeth. The objective of this study was to investigate the inhibitory effect of zinc on collagen degradation. METHODS Human dentin was ground and demineralized by citric acid (pH 2.0). The demineralized ground dentin was incubated in six different media: artificial saliva (AS); 5 mg/ml doxycycline in AS; 3.33, 6.82, 13.63, and 27.26 mg/ml of zinc chloride (Zn) in AS. Each group was divided into two subgroups, and active MMP-2 was incorporated into one subgroup. Specimens were incubated for 24 h, 1 week, and 2 weeks. Collagen degradation product was assessed using ELISA. The results were analyzed using repeated measured ANOVA and Duncan's post hoc analysis (α = 0.05). RESULTS The amount of collagen degradation was the lowest in Doxy group. Zn groups showed a significant inhibitory effect in collagen degradation for all concentrations (P < 0.05). In subgroups without exogenous MMP-2, zinc-mediated inhibition increased in a concentration-dependent manner with increasing zinc concentration. The amount of collagen degradation product slightly increased with increased incubation time from 24 h to 2 weeks. However, in subgroups with exogenous MMP, the inhibitory effect of zinc on collagen degradation did not depend on zinc concentration. CONCLUSIONS All Zn groups for the four concentrations tested exhibited statistically significant inhibitory effect on collagen degradation.