Evidences about the biosynthesis of secondary metabolites from plants point to constitutive or induce chemical defense generated for protection against to different phytopathogenic attack. Calceolaria spp. is regarded both as a notorious weed and as a popular ornamental garden plant and have medicinal application. Some taxa of the America distributed Calceolaria genus are toxic to insects, fungi and several bacteria strains, and its effect has been associated with the presence of phenolics. Calceolaria spp. produces a number of iridoids, flavonoids, naphthoquinones and phenylpropanoids that have been shown to possess interesting biological activities. All these aspects are considered in this review to allow an evaluation of the potential for utilization of the large biodiversity of Calceolaria available. An up-to-date of the phytochemistry and biological activities of several members of the Calceolariaceae family is show. New iridoids, flavonoids and phenylpropanoids for these Calceolaria species have been isolated, identified and tested for their antifeedant, igr, insecticidal, antimicrobial, anticancer, proteinase, tyrosinase, and acetylcholinesterase inhibitory activities. Until now mixtures of flavonoids have been found to be potent insecticides and fungicides, followed by phenylpropanoids mixtures and iridoids showed to be antifeedant and in some cases repellent and attractant. Dose-dependent experiments shows that flavonoids are insecticidal against S. frugiperda and D. melanogaster at early growth stages. Bactericidal and fungicidal activity showed that dunnione (a naphthoquinone) have potent activity as fungistatic and fungicidal. O-methylflavonols, and different mixtures of them were very effective fungistatic. However, fungistatic quercetin and dunnione both combined with sublethal amount of kaempferol and gallic acid showed a strong fungicidal activity against phytopathogenic strains. Additionally, naphthoquinones possess a promissory activity as anticancer.