The chemotherapy success to kill cancer cells depends on its ability to stop cell division. The faster the cells are dividing, the more likely it is that chemotherapy will kill the cells, causing the tumor to shrink. Taking into account the severe side effects of chemotherapy, drugs producers also focus on natural products obtained either from medicinal plants, or from microorganisms. The complex polysaccharides named beta-glucans are active compounds with immune activity. beta-glucan polymers belong to a class of drugs with effects on the immune system, such as: anti-tumoral, anti-infectious, protection against fungi, bacteria and viruses infections. The correct selection of beta-glucans is essential to identify compounds with favorable clinical effects. The aim of this study was to investigate the capacity of six Curdlan (beta-glucan) derivatives to up-regulate the Doxorubicin, Actinomycin D and Cyclophophamide cytostatic drug activity on tumor cells (murine B16 melanoma and human HEp-2 laryngeal carcinoma cell lines). Our results demonstrated that Palm SP derivative, as well as SP and Palm CM/SP derivatives were able to potentiate Doxorubicin action or Actinomycin D effect on B16 tumor cells. SP derivative significantly enhanced cytostatic activity of Cyclophosphamide on B16 cells. All the investigated Curdlan derivatives (SP, Palm CM/SP, CM/SP, Palm CM, Palm SP and CM) were able to inhibit HEp-2 tumor cell growth, by up-regulating Doxorubicin and Actinomycin D cytostatic activity.