Recently, the application of natural biocompatible polymeric hydrogels for the conception of drug delivery matrices has attracted widespread interest. Thus, in the present study, riboflavin pH-sensitive drug delivery hydrogels were developed based on blue crab chitosan (Cs), via direct dissolution in alkali/urea aqueous solution at low temperatures. First, the effect of Cs characteristics in terms of acetylation degree (AD) and molecular weight (Mw) on the structural, mechanical, thermal, swelling and in vitro biodegradation of Cs-based hydrogels were studied. Data from overall analysis revealed that Cs with low AD and high Mw exhibited improved mechanical properties, as evidenced by the compressive and rheological behaviors tests, thermal resistance, swelling behavior and in vitro degradation kinetics. However, hydrogels pore sizes were reduced with the AD decrease and Mw increase. Additionally, hydrogels in PBS (pH 5.5) underwent quicker degradation, compared to those immersed in PBS (pH 7.4). In the drug delivery model, the kinetics of Riboflavin release, through the Cs-based hydrogels were monitored. The Riboflavin release exhibited typical deliverance patterns, with significantly higher released amounts in more acidic systems. Therefore, drug encapsulation within the conceived pH-sensitive Cs-based hydrogels could provide suitable and promoting microenvironment for drugs delivery.