In this study, the solar photo-Fenton (SPF) process was investigated for the degradation of doxycycline (DOX) using a solar compound parabolic collector (CPC) reactor and a borosilicate serpentine tube with an irradiated volume of 1.8 L. The influence of the operating parameters, such as H2O2, Fe2+ dosage, and DOX concentration, was investigated. The optimum H2O2, Fe2+ dosage, and DOX concentration were found to be 4, 0.1, and 0.06 mM, respectively. The results of photo-Fenton experiments fitted the pseudo-first-order kinetic equation (R2 = 0.99). The efficiency of the treatment under optimized conditions was analyzed by an HPLC analysis of the samples, chemical oxygen demand (COD), and total organic carbon (TOC). The results obtained showed that the solar photo-Fenton process achieved a DOX degradation of 95.07%, a COD elimination of 81.43%, and a TOC elimination of 73.05%. The phytotoxicity tests revealed a 73.32% decrease in the germination index of watercress seeds, demonstrating that the SPF process minimizes the toxicity of the chemical and did not have any negative impact on plant growth. Overall, the results of this study suggest that SPF is a promising technology for the removal of doxycycline from wastewater.