Bio-based packaging materials and efficient drug delivery systems are gaining attention, carboxymethyl cellulose (CMC) is one of the most soluble cellulose derivatives, is a good candidate material due to its biocompatibility, biodegradability, and reproducibility. However, CMC-based films are lack of sufficient mechanical properties, limiting its widespread application. In this paper, the molecular interactions between CMC and additives with different molecular structures have been studied with rheological method. The additives are chitosan and cellulose derivatives including O-carboxymethylated chitosan (O-CMCh), N-2-hydroxypropyl-3-trimethylammonium-O-carboxymethyl chitosan (HTCMCh), hydroxypropyltrimethyl ammonium chloride chitosan (HACC), cellulose nanofibers (CNC), and cellulose nanofibers (CNF). The influencing factors, such as molecular structure, concentration of additives and temperature on the rheological properties were studied, which results revealed the information intermolecular interactions. Based on the rheological properties, several systems were selected to prepare films, which show very good transparency, wettability, mechanical properties, biodegradability, and cytotoxicity. These good characteristics of the selected films also proved the good biocompatibility of CMC and chitosan and cellulose derivatives. This work will provide an idea to prepare CMC-based food packaging and effective drug delivery materials with specific properties.