There's a blase, desensitised, black-comedy sensibility to the treatment of horror, violence and sex in this movie which not only anticipates "Night of the Living Dead" a few years later, but also Tarantino's approach decades later, let alone the lesser inheritors of that approach.
There are plenty of moments in this extremely strange little picture which capture the same nightmare-logic of the family banquet scene in "Texas Chainsaw Massacre", or pretty much the whole of "Eraserhead". While "Spider Baby" is funny in a lot of places, and intended to be, the choice of a hereditary neurological disorder as the source of the horror elements, rather than one of the standard horror movie devices (vampire, werewolf, mad scientist, whatever) gives the movie a case of the creeps that starts early and never goes away.
The most bizarre thing in the movie, isn't the weird members of the central family (although they're plenty weird enough to be going on with), it's how director Jack Hill does some things efficiently, some with amazingly ambitious creativity, and others with an equally mind-boggling klutziness. Blame the budget for the latter, I'd guess.
Amidst some amazing performances, (the two sisters and the brother), some blaringly cheesy ones (most of the "straight" roles), Lon Chaney Jr and Carol Ohmart stand out. Chaney, who is evidently not in tiptop physical condition for (ahem) some reason, nonetheless plays completely straight, in a strange, tender-hearted role (particularly in the black comedy context here) which is probably his best work other than "Of Mice and Men". Ohmart has a blowsier version of the strange, nasty, sexy role she played as Vincent Price's wife in "The House on Haunted Hill", and she is one of the most unusual screen presences you'll ever see. One good character part in a moderately-budgeted studio picture with a decent director would have been enough to make her more than a footnote name known exclusively to horror movie nuts.
Sustained weird atmosphere, and a movie unlike any other. Rather than a horror movie, or black comedy per se, it's an exceptionally twisted adult fairy tale. Probably not as good-hearted as "Curse of the Cat People" or "Edward Scissorhands" in the same rough ball-park, but at least as memorable as either.