Glucocorticoids (GCs) are well known to exert broad‐based effects on metabolism, behavior and immunity. Their impaired synthesis and production lead to adverse health effects. Some environmental toxicants, including phthalate esters (PAEs), are associated with endocrine disruption. These endocrine‐disrupting chemicals (EDCs) also cause adrenal toxicity and alteration of GC biosynthesis and their functions. Using in silico tools of Schrodinger Maestro 9.4, we performed a molecular docking study of 32 ligands including PAEs of a known endocrine‐disrupting potential with the selected enzymes of the GC biosynthesis pathway (GBP) such as CYP11A1, CYP11B2, CYP19A1, CYP17A1, CYP21A2 and 3α/20β‐HSD. Binding affinities of the PAEs were compared with known inhibitors of these enzymes. Amongst PAEs, diphenyl benzene‐1, 2 – dicarboxylate (DPhP) showed the lowest docking score of −8.95616 kcal mol⁻¹ against CYP21A1. Besides, benzyl butyl benzene‐1,2‐dicarboxylate (BBzP), bis(7‐methylnonyl) benzene‐1,2 dicarboxylate (DIDP) and bis(2‐ethylhexyl) benzene‐1,2‐dicarboxylate (DEHP) also showed comparable molecular interaction with enzymes of GBP. DPhP showed a significant molecular interaction with different enzymes of GBP such as CYP21A1, CYP11A1 and CYP11B2. These interactions mainly included H‐bonding, hydrophobic, polar and van dar Waals' interactions. Interestingly, this in silico study revealed that certain PAEs have more inhibitory potential against enzymes of GBP than their respective known inhibitors. Such studies become more relevant in the risk assessment of exposure to mixtures of phthalate eaters. Copyright © 2016 John Wiley & Sons, Ltd.