Glycidylmethacrylate-modified dextran macromers (Dex-GMA) of different degrees of substitution (DS) were synthesized. The elastic modulus of the hydrogels produced using one-component and two-component macromer systems was measured using rheometry. When one macromer of DS 1/10 was used, a hydrogel modulus in the range of 0.2 Pa to 42 kPa was obtained by varying the Dex-GMA concentration from 80 to 200 mg/mL. When a mixture of two macromers of different DS (1/10 and 1/23) was used, a more uniform variation of modulus in the range of 0.4 Pa to 42 kPa was achieved by controlling the ratio of the two macromers. When dextran hydrogels were functionalized with fibronectin and immobilized onto glass substrates, the attachment, spreading, and growth of human aortic smooth muscle cells were modulated by the elastic properties of the dextran matrix. The dextran hydrogel system with tunable mechanical and biochemical properties appears promising for applications in cell culture and tissue engineering.