The OECD (Organization for Economic Cooperation and Development), World Health Organization, Food and Agriculture Organization of the United Nations, and Codex Alimentarius Commission have all played significant roles internationally in setting standards for and assessing the safety of genetically modified food products (Kitta, 2013). In particular, the substantial equivalent study has been formulated by the OECD for extensive comparative studies of essential macro- and micronutrients and anti-nutrients in GMO crops and their corresponding controls (OECD, 2004). Within just the last decade, many substantial equivalence studies have been performed to assess the safety of GMOs with respect to conventional counterparts (Xue, Yang, Liu, & Xue, 2012). Targeted analysis of known compounds of high nutritional quality have also been analyzed for biosafety comparison with genetically modified crops. More recently, non-targeted proteomics profiling has become a promising tool to comprehend the changes on a translation level due to integration of a particular gene. Newly expressed proteins can serve many important roles in trait improvement, while at the same time they may also act as toxins, anti-nutrient factors, or allergens and thus have detrimental effects on human or animal health. Therefore, comparative proteomics is another important strategy in the comprehensive assessment of genetically modified organisms (Xue et al., 2012). Here, we present the results of a comprehensive proteomic profile and nutritional quality assessment of genetically modified bacterial blight-resistant rice plant, Xa21, and the non-transgenic parent IR72 rice, and discuss the relevance of proteome changes in the overall nutritional efficacy of Xa21.