A carboxymethyl derivative of scleroglucan (Scl-CM) with a derivatization degree of 65 ± 5% was synthesized. The rheological behaviour of this novel polymer was studied and compared with that of the starting polymer. We observed that the charged moieties carried on the chains could prevent the triple helix formation of Scl. Scl-CM aqueous solutions behave like true polymer solutions up to 1% w/v, whereas above this concentration a weak gel behaviour was observed. CaCl2 addition to aqueous Scl-CM solutions led to a physical gel formation; the hydrogel strength was related to polymer and CaCl2 concentrations. Temperature sweeps, registered at 1 Hz on hydrogels differing in CaCl2 concentration, evidenced a gel → sol transition in the range of 30–40°C, depending on the molar ratio between carboxylic groups and Ca+2. In order to verify a possible use of these hydrogels as drug delivery systems, acyclovir was loaded into the network. Rheological analysis evidenced that the loaded drug can affect the hydrogel elastic modulus. The release of acyclovir in phosphate buffer was evaluated at different temperatures in order to assess the suitability of this novel drug delivery system in topical applications.