Here we report the reaction in the biphasic system of the in situ prepared selenols and thiols with 1,4-androstadiene-3,17-dione (1) or prednisone acetate (2) having α,β-unsaturated ketone as an electrophilic functionalization. The Michael-type addition reaction resulted to be chemo- and stereoselective, affording a series of novel steroidal selenides and sulfides. This is an example of a one-step, eco-friendly process that bypasses some of the main concerns connected with the bad smell and the toxicity of these seleno- and thio-reagents. Furthermore, we demonstrated that the proposed methodology offers the possibility to prepare libraries of steroids variously and selectively decorated with different organochalcogen moieties at the C1 position starting from 1,4-androstadienic skeletons and leaving unaltered the C4–C5 unsaturation. Based on the data reported in the literature the introduction of an organoselenium or an organosulfur moiety in a steroid could provide new interesting pharmaceutically active entities exerting anticancer and antimicrobial activities. In this optic, new synthetic strategies to efficiently prepare this class of compounds could be strongly desirable.