Organic amendments are being increasingly applied to agricultural soils as alternatives or complements to inorganic fertilizers. Organic amendments can increase the content of soil organic matter, concomitantly improving soil physical, chemical and biological properties. We evaluated the effect of the application of commercial vs. farm-made fermented liquid organic amendments, compared to mineral (NPK) fertilization, on corn yield and nutritional status, as well as on soil physicochemical and microbial properties as indicators of soil quality. In particular, we assessed the effect of two doses (optimal vs. suboptimal) and times of amendment application (basal dressing vs. basal + top dressing) for two consecutive growing seasons. Values of corn grain yield were lower in organically-amended plots than in those under NPK fertilization. At the optimal dose, the application of organic amendments led to significantly higher values of microbial activity (soil respiration; enzyme activities; potentially mineralizable N) and biomass (microbial biomass C, bacterial and fungal biomass), leading to an improvement in soil quality. The optimal application dose resulted in an enhanced soil nutrient pool. Conversely, soil properties were not significantly affected by the origin of the amendment (commercial vs. farm-made) or the time of application (basal dressing vs. basal + top dressing). 16S rRNA metabarcoding analysis revealed no significant changes in the diversity and composition of the soil prokaryotic communities between organically-amended and NPK-fertilized soils. It was concluded that the application of fermented liquid organic amendments at the optimal dose (according to the N requirements of corn) can be a beneficial agronomic practice for agricultural soil quality, posing a suitable alternative to mineral fertilization.