Polymers and their composites have recently attracted attention in both pharmaceutical and biomedical applications. Polyethylene glycol (PEG) is a versatile polymer extensively used in medicine. Herein, three novel PEG-based polymers that are pseudopolyrotaxane (PEG/α-CD) (1), titania–nanocomposite (PEG/TiO2NPs) (2), and pseudopolyrotaxane–titania–nanocomposite (PEG/α-CD/TiO2NPs) (3), were synthesized and characterized. The chemical structure, surface morphology, and optical properties of the newly materials were examined by FT-IR, 1H-NMR, SEM, and UV–Vis., respectively. The prepared polymers were used as drug carriers of sulfaguanidine as PEG/α-CD/Drug (4), PEG/TiO2NPs/Drug (5), and PEG/α-CD/TiO2NPs/Drug (6). The influence of these drug-carrying formulations on the physical and chemical characteristics of sulfaguanidine including pharmacokinetic response, solubility, and tissue penetration was explored. Evaluation of the antibacterial and antibiofilm effect of sulfaguanidine was tested before and after loading onto the prepared polymers against some Gram-negative and positive bacteria (E. coli, Pseudomonas aeruginosa, and Staphylococcus aureus (MRSA)), as well. The results of this work turned out to be very promising as they confirmed that loading sulfaguanidine to the newly designed polymers not only showed superior antibacterial and antibiofilm efficacy compared to the pure drug, but also modified the properties of the sulfaguanidine drug itself.