There are several reports on the prevalence and importance of milk allergens in the induction of allergic diseases, whereas its role in the induction of autoimmune disease was rarely studied. So, the present work aimed to study the diagnosis and the efficacy of oral antigen specific immunotherapy (OAIT) on two groups of autoimmune disease patients namely, rheumatic arthritis (RA), group II, and systemic lupus erythematosus (SLE), group III, who has allergens for milk as an effective treatment option. From the assessment of the data obtained and the clinical outcome of RA and SLE patients after food elimination strategy and milk immunotherapy, it was evident that there were significant reductions (P < 0.001) in the levels of total IgE, specific IgE, Rheumatic factor (R.F), C-reactive protein (C.R.P), Anti-nuclear antibodies (ANA) and anti-double stranded DNA antibodies (Anti-ds DNA) compared to pretreated levels. Moreover, the immunotherapy induced “blocking antibodies” by remarkable highly significant increasing in IgG, phagocytic inhibition test (PIT %), Complement component 3(C3), and Complement component 4 (C4) levels. More improvement was noticed in the SLE as a result of the immunotherapy. Conclusion: milk desensitization is a gained interest and a safe valuable effective treatment of autoimmune conditions in Egypt.