Organic impurities in the fermentation broth of antibiotic production impose great difficulties in the crystallization and recovery of antibiotics from the concentrated waste liquor. In the present laboratory study, the inhibitory effect of biopolymers on antibiotic crystallization was investigated using oxytetracycline (OTC) as the model antibiotic. Organic impurities separated from actual OTC fermentation waste liquor by ultrafiltration were dosed into a pure OTC solution at various concentrations. The results demonstrated that small organic molecules with an apparent molecular weight (AMW) of below 10,000 Da did not affect OTC crystallization significantly. However, large biopolymers, especially polysaccharides, in the fermentation waste caused severe retardation of crystal growth and considerable deterioration in the purity of the OTC crystallized. Atomic force microscopy (AFM) revealed that OTC nuclei formed in the solution attached to the surfaces of large organic molecules, probably polysaccharides, instead of being surrounded by proteins as previously thought. It is proposed that the attachment of OTC nuclei to biopolymers would prevent OTC from rapid crystallization, resulting in a high OTC residue in the aqueous phase. In addition, the adsorption of OTC clusters onto biopolymers would destabilize the colloidal system of organic macromolecules and promote particle flocculation. OTC crystallization would therefore take place with the precipitation of abundant organic impurities. Hence, the removal of polysaccharides and other biopolymers by ultrafiltration can be an effective means of improving the recovery of OTC and similar antibiotics by crystallization from the fermentation waste.