The presented paper deals with the analysis of potential differences between organic waste compost (CBD), vermicompost (CVER) and mineral fertilizer (MF; 27% of N) applications affecting the quality of arable soil by influencing microbial activity therein. The selected types of compost represent alternatives to conventional organic fertilizers, which are, however, not available to Czech and Slovak farmers in sufficient amounts. Their mutual comparison and the comparison with organic fertilizers aim to provide farmers further information about their influence on arable land and thus to give them the possibility of deciding on the most suitable amendments. To demonstrate the effect of these amendments, six variants were prepared: one without the addition of fertilizers; two variants with the addition of 40 Mg/ha of CVER and CBD; one variant with the addition of double dosed CVER (80 Mg/ha), and the remaining two variants were fertilized only with MF (0.22 Mg/ha) and with the combination of CVER (0.20 Mg/ha) and MF (0.11 Mg/ha). Substrate induced respiration (SIR), basal respiration (BS), microbial carbon (Cmic) and enzymatic activities (hydrolysis of fluorescein diacetate—FDA, dehydrogenase activity—DHA, and phosphatase activity—PA) were used to evaluate the effect of CBD, CVER and MF application on the soil quality. Both organic and mineral amendments affected BS and SIR. The highest BS and SIR rates were found in variants with compost application (CVER and CBD). All variants treated with the mineral fertilizer showed the lowest level of enzyme activities; lower by about 30% in comparison with variants where CVER, CBD and the combination of MF and CVER were applied. We found insignificant differences between the individual types of compost. More importantly, we compared the situation at the beginning of the experiment and after its end. It was found that the application of mineral fertilizers automatically led to the deterioration of all enzymatic parameters, on average by more than 25%, as compared with the situation at the beginning of the experiment. However, when the mineral fertilizer dose was supplemented with organic amendments (CVER), this negative effect was eliminated or significantly reduced. Furthermore, both composts (CVER and CBD) positively affected plant biomass production, which reached a level of production enhanced by the MF. Results clearly showed that the application of both compost types could be used to improve soil quality in agriculture.