Seed persistence in the soil is threatened by microorganisms, but the seed coat helps protect the seed from them. Although modern rice (Oryza sativa L.) cultivars have a whitish caryopsis, some varieties have a red caryopsis coat, a trait typical of wild Oryza species. The red colour is due to the oxidation of proanthocyanidins, a class of flavonoids that is found in the outer layers of the seed in many species. We aimed to assess whether these natural compounds (proanthocyanidins and proanthocyanidin-derived pigment) have some protective effect against microbial attacks. Dehulled caryopses of white-grained and red-grained rice genotypes were employed to assay fungal infection. Specifically, three white-grained rice cultivars (Perla, Augusto, and Koral) and three red-grained rice varieties (Perla Rosso, Augusto Rosso, and Koral Rosso) were used. In a first test, the caryopses were infected with Epicoccum nigrum at 10 °C, and seedling growth was then assessed at 30 °C. In a second test, the degree of infection by the mycotoxigenic fungus Fusarium sporotrichioides was assayed by measuring the accumulation of T-2/HT-2 toxins in the caryopses. Infection was performed at 10 °C to prevent rice germination while allowing fungal growth. In both the tests, red caryopses showed reduced, or delayed, infection with respect to white ones. One black-grained cultivar (Venere) was assayed for the accumulation of T-2/HT-2 toxins as well, with results corresponding to those of the red-grained rice varieties. We argue that the red pigment accumulating in the caryopsis coat, and/or the proanthocyanidins associated with it, provides a protective barrier against challenging microorganisms.