Worldwide population is aging, and a large part of the growing burden associated with age-related conditions can be prevented or delayed by promoting healthy lifestyle and normalizing metabolic risk factors. However, a better understanding of the pleiotropic effects of available nutritional interventions and their influence on the multiple processes affected by aging is needed to select and implement the most promising actions. New methods of analysis are required to tackle the complexity of the interplay between nutritional interventions and aging, and to make sense of a growing amount of -omics data being produced for this purpose. In this paper, we review how various systems biology-inspired methods of analysis can be applied to the study of the molecular basis of nutritional interventions promoting healthy aging, notably caloric restriction and polyphenol supplementation. We specifically focus on the role that different versions of network analysis, molecular signature identification and multi-omics data integration are playing in elucidating the complex mechanisms underlying nutrition, and provide some examples on how to extend the application of these methods using available microarray data.