Here we combined microcalorimetry, enzyme activity measurements, and characterization of metal form in order to evaluate the effect of metal(loid)s on the activity of microbial community inhabiting tailings area with high toxic metal(loid)s concentration. Chromium (Cr), nickel (Ni), copper (Cu) and manganese (Mn) were the main pollutants. The exchangeable fractions (bioavailability) of Cu, Ni and Mn were higher in the tailings sample (Site Z), indicating a higher environmental risk. The total heat Qtotal (17,726.87 J/g), peak power Ppeak (541.42 μW/g) and growth rate constant k (0.11 h−1) of Site Z were higher than that of the polluted soil around tailings (Site Y). Such observation may be explained by physiological changes within the microbial community in response to high levels of heavy metal stress, thereby increasing respiration and improving microbial activity. In contrast, enzyme activities and enzyme activities index (GmeA) of Site Z were lower than the Site Y, which is strongly influenced by changes on physical-chemical properties (TN and TOC) and the presence of Cr, Mn, and Ni. Correlation coefficient and principal component analysis (PCA) indicate that GmeA is significantly correlated (p < 0.05 or p < 0.01) with environmental factors (EC, TOC and TN), Mn and Ni concentration, Ni bioavailability, and peak time (Tpeak). Therefore, GmeA represents a potential biological indicator for reporting the pollution degree in tailings area. Our results provide a theoretical basis for the prevention and control of pollution in non-ferrous metal(loid) tailings area