There is a considerable global increase in the manufacturing and abuse of designer drugs (structurally & pharmacodynamically resemble the illegal/banned psychostimulants).  Specifically, Piperazine designer drugs were designed as an alternative to 3,4-methylenedioxy-methamphetamine (ecstasy) and have shown to cause 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 the maternal-fetal dyad.  Nearly 5% of pregnant women abuse 1 or more substances during pregnancy in the USA.  These substances of abuse induce follicle depletion and enhance the possibility of developing lasting infertility and premature ovarian failure.  The use of Piperazine designer drugs among women are steadily increasing.  However, at present, the effect of Piperazine designer drugs 1-(3-trifluoromethylphenyl)-piperazine (3-TFMPP) & its structural congeners on ovarian toxicity are not well elucidated.  Hence, in this study we investigated the effect of Piperazine Designer Drugs on the ovarian toxicity.  Chinese hamster ovarian cells (CHO) are valid in vitro model to elucidate the toxic effects and determine the ovarian toxic mechanisms of Piperazine designer drugs & its structural congeners.  The parent drug, 3-TFMPP induced significant ovarian toxicity (induced dose and time dependent CHO cell death).  TFMPP derivatives-induced decreased prooxidants, decreased antioxidants, reduced mitochondrial function, increased pro-apoptotic activity, and induced inflammation.  Furthermore, the anxiety of retaliation and isolation precludes countless women from precisely describing the substance use patterns and receiving appropriate medical and psychological care.  Therefore, designer drugs use must be rigorously controlled, confined globally and valid patient education with appropriate pharmacotherapy should be developed immediately