Two types of new alginate-based wound dressings, Type-AP and Type-AE, were fabricated by the EDC-activated crosslinking of alginate with Polyethyleneimine and Ethylenediamine, respectively. As compared with the commercial non-woven wound dressing, Kaltostat®, both Type-AP and Type-AE dressings had higher degradation temperature, lower calcium content, and a sponge-like macroporous structure. In addition, these two alginate-based dressings had higher mechanical stress (12.37 ± 1.72 and 6.87 ± 0.5 MPa for Type-AP and -AE, respectively) and higher water vapor transmission rates (both about 3,500 g/m2/day) than KaltostatR (0.87 ± 0.12 MPa and 2,538 g/m2/day). Fibroblasts proliferated faster on these two newly developed wound dressings at a higher rate as compared with that on Kalostat® dressing. The results of animal study showed that the wounds treated with either Type-AP or Type-AE dressings healed faster than Kaltostat® with less encapsulation of residuals by fibrous tissue and more neo-capillary formation. These two newly developed Type-AP and Type-AE porous wound dressings thus have great potential for clinical applications.