Calorie restriction (CR) extends lifespan and delays onset of age-related diseases in various organisms, even when started later in life. Despite benefits for health and lifespan, CR’s negative impact on reproduction is documented in some animals. Studies employing approximately 40% CR detected a delay in sexual maturation and impairment of fertility, which were combined with extension of the reproductive period. In contrast, mild CR (10-20%) is apparently not deleterious to reproduction. Hence, we hypothesized that mild CR started at 8 months of age would prolong reproductive capabilities and improve health parameters of male mice. To test this hypothesis, we assessed the effects of 10 and 20% CR on reproductive organ weights, selected plasma parameters and hepatic/testicular gene expression in normal male mice of heterogeneous genetic background. Starting at 8 months of age (adult), mice were assigned to 3 regimen groups: 10% CR (n = 8), 20% CR (n = 9) or ad libitum (AL; n = 8). Four months of CR were sufficient to reduce glycemia in a non-fasted protocol. Mild CR initiated in adulthood did not significantly impact final body weight, most of the analyzed plasma parameters or weight of androgen-dependent organs. Moreover, CR did not interfere with expression of the assessed testicular genes, or most of the hepatic genes, but it did cause an increase in the levels of peroxisome proliferator-activated receptor gamma (Pparg) and mouse sulfotransferase (mSTa); and a decrease in glucose-6-phosphatase-α (G6pc) mRNA, which might signify improvement of body condition. The important finding of our study was that a mild CR regimen, as low as 10 and 20%, was sufficient to impair glycemia in a non-fasted state, and also the levels of plasma IGF-1, corroborating the concept that mild CR has the potential for improving health and longevity, even when started later in life.