The scope of the biocatalytic hydrogenation of alpha,beta-unsaturated compounds is extended by the less studied flavin-independent Medium and Short chain Dehydrogenases / Reductases. The subfamilies MDR002 and SDR114C do not contain any bound coenzymes, therefore they catalyse oxygen-insensitive NADPH-linked double bond reduction. Biotransformation screening of the SDR114C ene-reductase IPR showed a limited, monoterpenoid-like substrate scope. Out of six products formed, the highest yields were observed with isopulegone, levodione and 3,3,5-trimethyl cyclohexanone. Verbanone and pulegone were only produced by IPR and not by any flavin-dependent enzyme tested. SDR114C ketoreductases MMR and MNMR reduced the C=O bond of menthone, isomenthone and 3,5-dimethyl-2-cyclohexen-1-one, not performing any ene-reduction. The crystal structures of IPR and MNMR highlighted a key active site residue difference and mutated variants revealed a switch between ketoreduction and ene-reduction. The MDR002 ene-reductase subfamily revealed a more promising substrate scope, including bulky, straight chain and hydrophobic molecules (trans-cinnamaldehyde, benzalacetone, trans-2-nonenal) and substrates not reduced by the established OYE ene-reductases (pulegone, dihydro-alpha-ionone) or with opposite product enantioselectivities (alpha-methyl-trans-cinnamaldehyde, (S)-perillaldehyde). The 13 MDRs were chosen from in silico studies using a previously studied enzyme as a reference. The different key active site residues and the distal location of the homologues on a phylogenetic tree were identified. The reported data make MDR002 an interesting family for further studies, providing an alternative solution when the OYEs are not showing the desired activity under aerobic reaction conditions.