This study reports the in situ hemisynthesis of two novel dipyrromethanes (DPM-1 and DPM-2) from ethyl 1,2-dimethyl-1H-pyrrole-3-carboxylate and natural aldehydes: perillaldehyde from Ammodaucus leucotrichus and cuminaldehyde from cumin seed essential oil. The compounds were synthesized via a double Friedel-Crafts reaction under two catalytic systems: (i) water/ethanol (1:1 v/v) with 0.18 M HCl, and (ii) iodine-catalyzed chloroform. Structural elucidation was achieved using ¹H NMR,¹³C NMR, HSQC, HMBC, and HR-MS. Both derivatives showed significant inhibitory activity against AChE and BChE. DPM-2 was more active against AChE (IC₅₀ = 22.6 ± 0.06 μM) than DPM-1 (IC₅₀ = 51 ± 1.74 μM), and comparable to Galantamine (IC₅₀ = 21.81 ± 1.15 μM). Regarding BChE, DPM-2 (IC₅₀ = 115 ± 1.91 μM) exhibited greater inhibitory potency than DPM-1 (IC₅₀ = 230.41 ± 0.75 μM), and remained close to Galantamine (IC₅₀ = 120.93 ± 1.99 μM). In silico analysis supported their potential as anti-Alzheimer's agents.