Long-term use of inorganic fertilizers can increase soil acidity, be harmful to the environment, and leaving bad effects on human health. Organic fertilizer application is one of the safer alternatives with numerous benefits, such as supplying nutrients for plant growth. Sunflower is one of the most important grown oilseed crops in the world. Sunflower plants need a supply of essential nutrients for their optimal growth. As a result, the aim of this research is to explore the effect and mechanism of two organic fertilizers from different sources (sugarcane bagasse ash (SBA), compost coupled with biofertilizer (CCB)) and NPK inorganic fertilizer as a control on enzyme activity, physiological traits, and the uptake of mineral contents and heavy metals in sunflower plant (Helianthus annuus L.). Fresh or dry mass (FM, DM), osmolytes and secondary metabolites, photosynthesis pigments, and enzymatic and non-enzymatic antioxidant molecules were all determined. Both sugarcane bagasse ash and compost coupled with biofertilizer resulted in a high value of fresh and dry mass, plant height, and chlorophyll content. The results revealed that the use of sugarcane bagasse ash (SBA) and compost coupled with biofertilizer increased osmolyte contents (soluble proteins and soluble sugars), antioxidants system enzyme/molecule (catalase, superoxide dismutase, peroxidase, and TGS) and secondary metabolites. However, the highest value of proline, total free amino acids, and phenolic compounds in sunflower plants was determined after NPK fertilizer application. On the contrary, it lowered Na, Na/K ratio, and Cd content. Data showed that organic fertilizers enhanced the accumulation of Cl, PO4, and SO4 content in sunflower plants. Generally, CCB and SBA treatments increased Cu, Zn, and Pb accumulation in sunflower plants. Using organic fertilizers with chemical NPK fertilizer can improve the chemical, physical, and biological soil properties.