Schistosomiasis represents a public health problem and praziquantel is the only drug used for treatment of all forms of the disease. Thus, the development of new anti-schistosomal agents is of utmost importance to increase the effectiveness, reduce side effects and delay the emergence of resistance. The present study was conducted to report the therapeutic efficacy of PPQ-8, a new synthetic quinoline-based compound against Schistosoma mansoni. Mice were treated with PPQ-8 at day 49 post infection using two treatment regimens (20 and 40 mg/kg). Significant reductions were recorded in hepatic (62.9% and 83.6%) and intestinal tissue egg load (57.4% and 73.5%), granuloma count (75.4% and 89.1%) and diameter (26.2% and 47.3%), in response to the drug regimens, respectively. In addition, both treatment regimens induced significant decrease in liver (23.3% and 32.8%) and spleen (37.5% and 45.3%) indices. Also, there were significant reductions in mature ova, total worm and female count, which were more prominent with the higher dose. The reduction in the level of nitric oxide in the liver by both therapeutic regimens to 22.5% and 47.2% indicates the anti-oxidant activity of PPQ-8. Bright field microscopic examination of worms recovered from infected and PPQ-8-treated mice showed nearly empty intestinal caeca with no observable changes in the tegument. Our findings hold promise for the development of a novel anti-schistosomal drug using PPQ-8, but further in vitro and in vivo studies are needed to elucidate the possible mechanism/s of action and to study the effect of PPQ-8 on other human schistosomes.