We present the use of root zone treatment (RZT) based system for the removal of pharmaceutical and personal care products (PPCPs) from domestic wastewater. The occurrence of more than a dozen PPCPs were detected in an academic institution wastewater treatment plant (WWTP) at three specific locations, i.e., influent, root treatment zone, and effluents. The comparisons of observed compounds detected at various stages of WWTP suggest that the presence of PPCPs, like homatropine, cytisine, carbenoxolone, 4,2′,4′,6′-tetrahydroxychalcone, norpromazine, norethynodrel, fexofenadine, indinavir, dextroamphetamine, 3-hydroxymorphinan, phytosphingosine, octadecanedioic acid, meradimate, 1-hexadecanoyl-sn-glycerol, and 1-hexadecylamine, are unusual than the usual reported PPCPs in the WWTPs. In general, carbamazepine, ibuprofen, acetaminophen, trimethoprim, sulfamethoxazole, caffeine, triclocarban, and triclosan are often reported in wastewater systems. The normalized abundances of PPCPs range between 0.037–0.012, 0.108–0.009, and 0.208–0.005 in main influent, root zone effluent, and main effluents, respectively, of the WWTP. In addition, the removal rates of PPCPs were observed from −200.75% to ∼100% at RZT phase in the plant. Interestingly, we observed several PPCPs at later stages of treatment which were not detected in the influent of the WWTP. This is probably owing to the presence of conjugated metabolites of various PPCPs present in the influent, which subsequently got deconjugated to reform the parent compounds during the biological wastewater treatment. In addition, we suspect the potential release of earlier absorbed PPCPs in the system, which were absent on that particular day of sampling but have been part of earlier influents. In essence, RZT-based WWTP was found to be effective in removing the PPCPs and other organic contaminants in the study but results in stress the need for further comprehensive research on RZT system to conclude the exact removal efficacy and fate of PPCPs during treatment in the system. As a current research gap, the study also recommended RZT to be appraised for PPCPs in-situ remediation from landfill leachates, an underestimated source of PPCPs intrusion in the environment.