There is a considerable global increase in the manufacturing and abuse of New Psychoactive Substances (NPS) / Designer Drugs (DD-drugs that structurally & pharmacodynamically resemble illegal/banned psychostimulants). Specifically, Piperazine designer drugs were designed as an alternative to 3,4-methylenedioxymethamphetamine (MDMA) and caused several toxic consequences leading to vast health concerns, safety & law enforcement issues, and lethality. Addiction to substances of abuse during pregnancy causes severe undesirable health consequences for both the mother and fetus. Nearly 5% of pregnant women abuse one or more substances during pregnancy in the USA. These substances of abuse affect ovaries by inducing follicle depletion and enhancing the possibility of developing lasting infertility and premature ovarian failure. The use of Piperazine designer drugs and their structural congeners among women is steadily increasing. However, the effect of Piperazine designer drugs 1-(3-trifluoromethylphenyl)-piperazine (3-TFMPP) & their structural congeners on ovarian toxicity are not well known. Hence, in this study, we elucidated the effects of Piperazine Designer Drugs on ovarian cells using Chinese hamster ovarian cells (CHO), which are valid in vitro models used to investigate mechanisms of toxicity and their effects. The parent drug, 3-TFMPP, induced significant ovarian toxicity (induced dose and time-dependent CHO cell death). The derivatives of TFMPP caused oxidative stress, reduced mitochondrial function, increased pro-apoptotic activity, and induced inflammation. Furthermore, the anxiety of retaliation and isolation precludes countless women from precisely describing their substance use patterns and receiving appropriate medical and psychological care. Therefore, New Psychoactive Substance/Designer Drug use must be rigorously controlled, confined globally, and valid patient education with appropriate pharmacotherapy should be developed immediately.