Antioxidants (AOs) are increasingly detected in the environment, in aquatic organisms, and in human biosamples. Therefore, we performed a comprehensive environmental and human health hazard assessment of more than 500 natural and synthetic AOs by exploring hazards associated with them, i.e., recalcitrance towards mineralization (NRB), persistence (P), bioaccumulation (B), toxicity (T), mobility (M), and formation of toxic transformation products (TPs). Experimental data complemented with in silico predictions revealed that 60% of the AOs classify/ are predicted to classify as NRB and T, out of which 31.6% classify as P and T. Of highest concern following EU regulations are PBT or PMT compounds, which are 4.8% and 2.1% of the AOs studied, respectively. All AOs classified as PBT/ PMT are of synthetic origin and by majority primary AOs, i.e., phenolic or amine compounds. Further, most predicted toxic TPs stem from phenolic and amine AO parent compounds. Natural primary AOs or secondary AOs, such as ester or organic sulfur compounds, are less often classified as hazardous. Only 19 AOs were identified as “non-hazardous”, with two still predicted to form at least one toxic TP.