Two new families of thermo-responsive and enzymatically degradable nanogels were synthesized by batch emulsion polymerization of N-vinylcaprolactam (VCL) with dextran methacrylates (Dex-MA) with different degrees of substitution (DS). The first family was prepared using different amounts of Dex-MA with high DS forming highly cross-linked nanogel particles with the typical thermal behavior of PVCL-based nanogels: below the volume phase transition temperature (VPTT) nanogel particles were swollen and above it they were collapsed. After their enzymatic degradation with dextranase, nanogel particles swelled due to the cleavage of some glucopyranosyl bonds of dextran, but preserved their identity. On the other hand, the second family was prepared using different amounts of Dex-MA with low DS forming slightly cross-linked nanogel particles with an anomalous thermal behavior. Surprisingly, above the VPTT of the nanogel particles monodisperse interparticle reversible aggregates were formed. In addition, after their enzymatic degradation, a release of reducing sugars together with an intense de-swelling due to the fragmentation of the nanogel structure was observed. Both nanogel families could be suitable for drug delivery in tissues or organs where dextranase is present.