Excessive fluoride concentration in potable water can lead to fluorosis of teeth and bones. In the present study, Donnan dialysis (DD) is applied for the removal of fluoride ions from diluted sodium fluoride solutions. A four factor two level (24) full factorial design was used to investigate the influence of different physico-chemical parameters on fluoride removal efficiency (YF) and fluoride flux (JF) through anion exchange membrane. The statistical design determines factors which have the important effects on Donnan dialysis performance and studies all interactions among the considered parameters. The four significant factors were initial fluoride concentration, feed flow rate, temperature and agitation speed. The experimental results and statistical analysis show that the temperature and agitation speed have positive effects on fluoride removal efficiency and the initial fluoride concentration has a negative effect. In the case of fluoride flux, feed flow rate and initial concentration are the main effect and all factors have a positive effect. The interaction between studied parameters was not negligible on two responses. A maximum fluoride removal of 75.52% was obtained under optimum conditions and the highest value of fluoride flux obtained was 2.4 mg/cm2·h. Empirical regression models were also obtained and used to predict the flux and the fluoride removal profiles with satisfactory results.