This article aims to formulations and properties of novel hybrid biomaterials containing unique four-phase combinations of polylactide (PLA), nanoclays, flax fibers, and coupling agents. A PLA-grafted maleic anhydride (PLA-g-MA) masterbatch containing 10 wt% PLA-g-MA was obtained by reactive extrusion and was further used, after dilution, as a coupling agent. In addition, three PLA masterbatches containing 10 wt% of three different grades of nanoclays, one untreated nanoclay and two organonanoclays, were also compounded. In a subsequent extrusion step, the nanoclay masterbatches were diluted in PLA down to 4 and 2 wt% while simultaneously incorporating in each one 20 wt% of short flax fibers. Those bio-nanocomposites were compounded without and with an equivalent content of PLA-g-MA, that is, with 4 and 2 wt%, respectively, through the dilution of 10 wt% PLA-g-MA masterbatch. The effects of the nanoclay chemistries, PLA-g-MA, and of flax fibers presence on the properties of bio-nanocomposite hybrid materials were investigated. X-ray diffraction, scanning electron microscopy, transmission electron microscopy, rheology, mechanical properties (tension, flexural, and Izod impact), and reprocess ability tests were used to characterize the bio-nanocomposite hybrid materials. In a second step, PLA-g-MA was replaced by an epoxy/styrene/acrylic copolymer for comparison purpose of their respective effect in bio-nanocomposite performances. Mechanical properties of bio-nanocomposites containing the second coupling agent were also evaluated. The effect of the epoxy/styrene/acrylic copolymer is discussed in comparison with the effect of PLA-g-MA.