Plantain prices in sub-Saharan markets are very high due to the fact that the supply does not cover the large demand. The main constraint of plantain cultivation is the seedlings unavailability in quantity and quality, which is essential to boost the creation of new plantations. The PIF technique could solve this problem if its substrate of production is amended with natural products for quality enhancement. This study aims to assess clam shells and Tithonia diversifolia effects on the growth of PIF plantain seedlings and their sensitivity to Mycosphaerella fijiensis. Plantain PIF seedlings were grown in an amended substrate. The treatment influences the seedlings germination rate, number of shoots, height, diameter, area of leaves and favours a less sensitivity to M. fijiensis compared to the controls. The presence of clam shells and T. diversifolia in the treatment especially enhanced the (1) vegetative growth and (2) less sensitivity as well as accumulation of proteins and polyphenols respectively. This combination shows a synergic action with dual role both as a biofertilizer and as a biopesticide. This work valorises the use of by-fishing products and bad herbs that are environmentally benign and affordable to poor smallholders' farmers, leading to a sustainable and responsible agriculture, as well as poor peasants' empowerment.