Natural Cr-(III)-organic species are being known as the part of natural biogeochemical cycle of chromium, but unfortunately, their mechanism of toxicity as well as genotoxic potentiality is still unknown. To evaluate the characteristic toxic effect exerted by natural Cr-(III)-organic species on the cellular macromolecules, changes in DNA and protein level was observed. Besides, Comet assay was applied to measure genotoxic potentiality of Cr-(III)-organic species in the target organism Saccharomyces cerevisiae exposed to Cr-(III)-citrate and Cr-(III)-histidine. It has been observed that both of the Cr-(III)-organic compounds are responsible for diminution in macromolecules concentration. Cr-(III)-citrate showed ladder pattern of DNA fragmentation in support of apoptosis. Two new protein bands appeared in protein profile of the Saccharomyces cerevisiae treated with Cr-(III)-organic compounds. Thus it supports the possibility of the synthesis of stress proteins. Comet assay proved positive correlation between Cr-(III)-organic compounds’ concentration and DNA damage. The Cr-(III)-citrate causes DNA damage at the concentrations ranging from 50 to 150 mg L−1, whereas the DNA damaging capacity of Cr-(III)-histidine was found insignificant, except at highest concentration (150 mg L−1). These results can throw light on the mechanism of the toxic effect as well as genotoxicity exerted by natural Cr-(III)-organic species.