Cadmium (Cd) is one of the most important stress factors in plants, with its high mobility in soils, ease of uptake by plants and toxicity at low concentrations. Aluminum (Al) is another phytotoxic metal, the accumulation of which is a crucial agricultural complication for plants, especially in acidic soils. In this study, Bryophyllum daigremontianum clone plantlets were obtained from bulbiferous spurs of a mother plant and separated into four different groups and watered with Hoagland solution and mixtures containing 0, 50, 100, and 200 µM of AlCl3 and CdCl2 each for 75 days. Control groups were maintained under the same conditions without Al and Cd treatment. To simulate acidic soil conditions typical of environments where Al toxicity is prevalent, the soil pH was adjusted to 4.5 by spraying the sulphuric acid (0.2%) with 2-day intervals after each irrigation day. After harvesting, growth parameters such as shoot length and thickness, root, shoot and leaf fresh and dry weights were measured, along with physiological parameters like mineral nutrient status, total protein, and photosynthetic pigment concentrations (chlorophyll a, b, a/b, total chlorophyll, and carotenoid) in both control and experimental groups of B. daigremontianum clones. In response to Al and Cd applications, the plant height, shoot thickness and carotenoid levels were declined, whereas the increments were found in leaf/shoot/root fresh weight, root dry weight, and total protein content. Moreover, differences in genomic alterations were investigated using 21 ISSR and 19 RAPD markers, which both have been used extensively as genetic markers to specify phylogenetic relationships among different cultivars as well as stress-dependent genetic alterations. RAPD primers were used due to their arbitrary sequences and the unknown genome sequence of the plant material used. In contrast, ISSR primers were preferred for a genome-wide genotoxic effect scan via non-arbitrary and more common genetic markers. Distinct types of band polymorphisms detected via RAPD and ISSR markers include band loss, and new band formation under a combination of Al and Cd stress. 17 ISSR and 14 RAPD primers generated clear electrophoretic bands. The study revealed that combined application of Al and Cd affect B. daigremontianum clones in terms of growth, physiology and genotoxicity related to the increasing concentrations.