Chitosan, a natural polysaccharide obtained from chitin deacetylation, complexes with metal ions by coordination with the free electron pairs of amine groups. Based on this complexation mechanism, cross-linked chitosan-metal microparticles were prepared by spray drying using iron (II or III) or zinc ions and characterized in terms of size distribution and capacity to specifically adsorb ciprofloxacin. Chitosan-Zn(II) and chitosan-Fe(III) microparticles appear to adsorb more ciprofloxacin than plain chitosan or chitosan-Fe(II) microparticles. Adsorption isotherms for CH and CH–Fe(II) microparticles can be fitted by a single logarithm model (slope 1) with one ciprofloxacin per adsorption site, whereas for CH–Fe(II) and CH–Zn(II) microparticles, isotherms are bilogarithmic with an initial slope of 2, suggesting that a single adsorption site can bind two molecules of ciprofloxacin. In addition, the pseudo second order kinetic model fits well experimental data, proving that adsorption is mediated by a chemical reaction. CH–Fe(II) and CH–Zn(II) appear very promising for drug elimination, either from hospital waste water or from the gastrointestinal tract to prevent the emergence of antibiotic resistance.