You can't set weapons to only work with one hand OR the other as you describe. But, you can set some weapons to permit off-hand weapons... like if you use the 'Dark Sword' in one hand, you can use a 'mythril dagger' in the other.
You'd label the Dark Sword as a weapon that needs an off-hand weapon. Off-hand weapons (I think) are weapons that are not classified as 'needs_offhand' (would cause a recursive error?) or are not classified as two-handed & such.