Food is fundamental for the survival of organisms, governing growth, maintenance, and reproduction through the provision of essential macronutrients. However, access to food with optimum macronutrient composition, which will maximize the evolutionary fitness of an organism, is not always guaranteed. This leads to dietary mismatches with potential impacts on organismal performance. To understand the consequences of such dietary mismatches, we examined the effects of isocaloric diets varying in macronutrient composition on eight key organismal traits spanning across the lifespan of a large outbred Drosophila melanogaster population (n ~ 2500). Our findings reveal that carbohydrate-reduced isocaloric diets correlates to accelerated pre-adult development and boosts reproductive output without impacting pre-adult viability and body size. Conversely, an elevated dietary carbohydrate content correlated to reduced lifespan in flies, evidenced by accelerated functional senescence including compromised locomotor activity and deteriorating gut integrity. Furthermore, transcriptomic analysis indicated a substantial difference in gene regulatory landscapes between flies subject to high carbohydrate vs high protein diet, with elevated protein levels indicating transcriptomes primed for reduced synthesis of fatty acids. Taken together, our study helps advance our understanding of the effect of macronutrient composition on life history traits and their interrelations, offering critical insights into potential adaptive strategies that organisms might adopt against the continual dietary imbalances prevalent in the rapidly evolving environment.