Desmodium canum (Strong back) commonly consumed as a tea or tonic is believed to possess hypoglycaemic activity. This paper sets out to isolate potential hypoglycaemic compounds present within the plant and investigate their synergistic effects on blood glucose levels in euglycaemic Sprague Dawley rats. The milled plant was sequentially extracted using hexane, ethyl acetate and methanol. The ethyl acetate extract was subjected to column chromatography yielding seven major fractions and were subsequently bioassayed using the Oral Glucose Tolerance Test (OGTT). Further chromatographic separation and analysis using Gas Chromatography–Mass Spectroscopy and Fourier Transform Infrared Spectroscopy enabled the identification of two hypoglycaemic compounds, oleic acid (OA) and succinic acid (SA). These were bioassayed individually and as a cocktail to determine the synergistic effects using OGTT. Intravenous administration of these compounds individually indicated both are very potent in retarding blood glucose levels. However, the most significant activity was observed on synergistic administration. The cocktail (1 : 1) displayed significant hypoglycaemic activity throughout the entire study. It also significantly differed from OA at the 120 min interval (3.43 ± 0.22 mmol/L vs. 4.98 ± 0.19 mmol/L, resp.,
p
=
4.29
×
10
−
7
) and significantly differed from SA at 30 min (3.95 ± 0.43 mmol/L vs. 5.17 ± 0.32 mmol/L, resp.,
p
=
0.003
), 90 min (4.35 ± 0.36 mmol/L vs. 5.49 ± 0.69 mmol/L, resp.,
p
=
0.04
), and 120 min intervals (3.43 ± 0.22 mmol/L vs. 4.94 ± 0.31, resp.,
p
=
1.54
×
10
−
5
). Oral administration of the cocktail showed comparable potency to that of metformin (
p
>
0.05
) throughout the OGTT curve. The synergistic effects of the naturally isolated compounds yielded higher potency levels than individual administration and when administered orally, the hypoglycaemic effect was similar to that of metformin. This may assist in paving a way to attempt a novel method in approaching antidiabetic therapy.