Honey, pomegranate juice, and lemon juice are natural plant growth bio-stimulators with many bioactive substances that play essential roles in many plants' physio-biochemical processes, and development. The objectives of this research were to explore how foliar spraying with a 5% or 10% diluted pomegranate juice solution (DPJS), diluted lemon juice solution (DLJS), or diluted honey solution (DBHS), versus a control (distilled water; D-H₂O), positively influenced the leaf integrity, RubisCO gene expression, secondary metabolites, and antioxidant activities in Calendula officinalis plants. Foliar spraying with 5% or 10% individually from each DPJS, DLJS, or BHS significantly increased leaf SPAD index, relative water content (RWC), membrane stability index (MSI), total soluble (TS) sugar and K⁺ contents, RubisCO content and activity, and RubisCO gene expression. Also, secondary metabolite and antioxidant capacity (total flavonoid, anthocyanin, proline, ascorbate, and glutathione contents) were significantly increased by foliar spraying of all the above-mentioned treatments. The second best treatment was 5%-DPJS or 10%-BHS, both of which were preceded by 5%-BHS as the best treatment, which the research results recommended for field application to obtain the best pharmaceutical contents from Calendula officinalis.