The global plasticizer market is projected to increase from $17 billion in 2022 to $22.5 billion in 2027. Various emerging/alternative plasticizers entered the market following the ban on several phthalate plasticizers because of their harmful effects. However, there are limited data (especially peer-reviewed) on emerging plasticizers’ toxicity and environmental impact. This review compiles available data on toxicity, exposure, environmental effects, and safe production of emerging plasticizers. It identifies gaps in scientific research and provides evidence that emerging plasticizers are potential cases of regrettable substitution. Several alternative plasticizers, such as acetyl tributyl citrate (ATBC), diisononyl cyclohexane-1,2 dicarboxylate (DINCH), tris-2-ethylhexyl phosphate (TEHP), tricresyl phosphate (TCP), tris-2-ethylhexyl phosphate (TPHP), bis-2-ethylhexyl terephthalate (DEHT), and tris-2-ethylhexyl trimellitate (TOTM), show potential endocrine-disrupting properties and other toxic characteristics. Some chemicals like bis-2-ethylhexyl adipate (DEHA), diisobutyl adipate (DIBA), ATBC, DINCH, bis-2-ethylhexyl sebacate (DOS), diethylene glycol dibenzoate (DEGDB), DEHT, and phosphate esters showed the potential to cause toxicity in aquatic species. Plus, there is great lack of information on compounds like diisononyl adipate (DINA), dibutyl adipate (DBA), diisodecyl adipate (DIDA), dipropylene glycol dibenzoate (DPGDB), dibutyl sebacate (DBS), alkylsulfonic phenyl ester (ASE), trimethyl pentanyl diisobutyrate (TXIB), DEGDB and bis-2-ethylhexyl sebacate (DOS). Some compounds like epoxidized soybean oil (ESBO), castor-oil-mono-hydrogenated acetate (COMGHA), and glycerin triacetate (GTA) are potentially safer or less toxic. Alternative plasticizers such as adipates (log K_ow 4.3–10.1), cyclohexane dicarboxylic acids (log K_ow 10), phosphate esters (log K_ow 2.7–9.5), sebacates (log K_ow 6.3–10.1), terephthalates (log K_ow 8.4), and vegetable oil derivatives (log K_ow 6.4–14.8) have log K_ow values that are comparable to phthalate plasticizers (log K_ow 7.5–10.4), indicating potential bioaccumulation and health consequences. Field studies have demonstrated that phosphate esters can undergo bioaccumulation and biomagnification, but there is a lack of bioaccumulation studies for other compounds. We also discuss the metabolism of emerging plasticizers, though data are limited. Our article highlights that numerous alternative compounds display potential health and ecological risks, indicating they might not be suitable substitutes for legacy plasticizers. There is also a lack of scientific data on most emerging plasticizers. This way, we call for increased research and timely regulatory action to prevent global contamination and health risks. Finally, this study presents a scientifically robust protocol to avoid harmful substitutions and ensure the production of safer chemicals.