This paper presents a comparison between jeans and FR4-based patch antenna sensors for blood glucose sensing using a noninvasive approach. The dual-feed square-patch antenna sensor with partial ground has a compact structure operating at 2.8 GHz frequency. The performance of the antenna sensor was evaluated by measuring the shifts in the resonant frequency with varying blood glucose concentrations in the simulations. Both antenna sensors were experimentally tested and validated by placing a human volunteer’s fingertip on the patch. The jeans-based antenna sensor exhibited higher sensitivity to glucose variations than the FR4 based antenna. This study demonstrated the crucial role of substrates in sensing applications involving interactions with human tissues.