In this article, two series of novel glitazones are reported for their synthesis, in vitro glucose uptake activity by the rat hemi-diaphragm, and in vitro cytotoxic activity against human carcinoma HEp-2 (epidermoid carcinoma of the larynx) and A549 (human lung cancer cell line) cells. Some of the compounds exhibit good glucose uptake and cytotoxic activities. Compound 5 with 2,4-dichlorophenol moiety connected to TZD via the two carbon linker has exhibited good glucose uptake activity. One of the compounds exhibits both cytotoxic and glucose uptake activities (compound 4). Illustrations about their synthesis, and in vitro glucose uptake and cytotoxic activities are described along with their structure–activity relationships.