In the present investigation, CaCO3 (nano-calcite) was prepared using a microwave-assisted sol-gel route and photocatalyst efficiency was investigated by degrading antibiotic, Erythromycin (Ery). The prepared sample was characterized by XRD, SEM, EDX, FTIR and UV–vis techniques. The process variables such as Ery concentration, irradiation time and catalyst dose were optimized by RSM (response surface methodology) techniques. The Ery degradation was achieved up to 93% (6 h sunlight) and 73% (2 h UV irradiation) at Ery concentration 30 mg/L and catalyst load 20 mg. The water quality parameters (COD, BOD and TOC) were also evaluated pre- and post-treatment and the COD, BOD and TOC values were reduced up to 78.5, 77.6, 64.5 (%), respectively. The reusability/recyclability of CaCO3 was also performed and up to 3 cycles the activity did not change, which reduced slightly for 4–9 cycles slightly at each run. The results indicate that CaCO3 is an efficient catalyst for the degradation of Ery under sunlight irradiation, which could be used for Ery degradation in effluents.