It is a matter of attitude, as much as physical size & strength
My mother was 4'11 1/2", weighed 90-100lbs, wore a size 3 1/2 ring, and could shoot my Dad's 6" S&W Model 28 .357 magnum. She could handle a Colt Govt model (1911A1) in .38 Super. These guns were not ideal for her, but she could do it.
She could not, however, manage an Ortgies .25acp. She did not have the gripping strength in her hands needed to rack the slide (with a small gripping area) against the fairly strong spring.
Her personal choice handgun was a Ruger Super Bearcat (.22LR). She did not ccw a pistol, but would open (holster) carry the Bearcat from time to time. She was comfortable (and quite accurate) with the gun. Also, she was competent with a double barrel 12 ga shotgun, which she would fire "from the hip". Between these two, she felt adequately armed for home defense. I also saw this woman corner an 1,100lb angus bull, and hold it at bay for a couple hours (until Dad got home) with just a pitchfork, when I was a young boy. Its a lot about attitude, and a little about knowing how to do it.
Your wife's gun should be something she is comfortable with, and can operate easily. The specific caliber is the least important factor. Personally, I would see if she can get comfortable with the balance of a mid size .38/.357 revolver. Custom grips and an action/trigger job could make a world of difference. But any gun, even a .22 that she is willing to use, and feels confidence in her abilities with, is better than no gun, or a gun she isn't happy with.